@article{pmid15211524,

title = {Crystal structure of a methionine aminopeptidase (TM1478) from Thermotoga maritima at 1.9 A resolution},

author = {Glen Spraggon and Robert Schwarzenbacher and Andreas Kreusch and Daniel McMullan and Linda S Brinen and Jaume M Canaves and Xiaoping Dai and Ashley M Deacon and Marc-André Elsliger and Said Eshagi and Ross Floyd and Adam Godzik and Carina Grittini and Slawomir K Grzechnik and Lukasz Jaroszewski and Cathy Karlak and Heath E Klock and Eric Koesema and John S Kovarik and Peter Kuhn and Timothy M McPhillips and Mitchell D Miller and Andrew Morse and Kin Moy and Jie Ouyang and Rebecca Page and Kevin Quijano and Fred Rezezadeh and Alyssa Robb and Eric Sims and Raymond C Stevens and Henry van den Bedem and Jeff Velasquez and Juli Vincent and Frank von Delft and Xianhong Wang and Bill West and Guenter Wolf and Qingping Xu and Keith O Hodgson and John Wooley and Scott A Lesley and Ian A Wilson},

doi = {10.1002/prot.20084},

issn = {1097-0134},

year  = {2004},

date = {2004-08-01},

journal = {Proteins},

volume = {56},

number = {2},

pages = {396--400},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15211526,

title = {Crystal structure of a PIN (PilT N-terminus) domain (AF0591) from Archaeoglobus fulgidus at 1.90 A resolution},

author = {Inna Levin and Robert Schwarzenbacher and Rebecca Page and Polat Abdubek and Eileen Ambing and Tanya Biorac and Linda S Brinen and Jamison Campbell and Jaume M Canaves and Hsiu-Ju Chiu and Xiaoping Dai and Ashley M Deacon and Mike DiDonato and Marc-André Elsliger and Ross Floyd and Adam Godzik and Carina Grittini and Slawomir K Grzechnik and Eric Hampton and Lukasz Jaroszewski and Cathy Karlak and Heath E Klock and Eric Koesema and John S Kovarik and Andreas Kreusch and Peter Kuhn and Scott A Lesley and Daniel McMullan and Timothy M McPhillips and Mitchell D Miller and Andrew Morse and Kin Moy and Jie Ouyang and Kevin Quijano and Ron Reyes and Fred Rezezadeh and Alyssa Robb and Eric Sims and Glen Spraggon and Raymond C Stevens and Henry van den Bedem and Jeff Velasquez and Juli Vincent and Frank von Delft and Xianhong Wang and Bill West and Guenter Wolf and Qingping Xu and Keith O Hodgson and John Wooley and Ian A Wilson},

doi = {10.1002/prot.20090},

issn = {1097-0134},

year  = {2004},

date = {2004-08-01},

journal = {Proteins},

volume = {56},

number = {2},

pages = {404--408},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15250702,

title = {Covalent display of oligosaccharide arrays in microtiter plates},

author = {Marian C Bryan and Fabio Fazio and Hing-Ken Lee and Cheng-Yuan Huang and Aileen Chang and Michael D Best and Daniel A Calarese and Ola Blixt and James C Paulson and Dennis Burton and Ian A Wilson and Chi-Huey Wong},

doi = {10.1021/ja048433f},

issn = {0002-7863},

year  = {2004},

date = {2004-07-01},

journal = {J Am Chem Soc},

volume = {126},

number = {28},

pages = {8640--8641},

abstract = {A covalent array for the display of complex oligosaccharides in microtiter plates has been developed. This strategy is conducive to the display of carbohydrates to proteins of interest such as lectins and antibodies, including the broadly neutralizing antibody 2G12 against HIV envelope oligomannose and can be cleaved from the surface for further characterization by mass spectrometry. The system was used to probe the multivalent interaction of 2G12 with an optimal epitope (Kd 0.1 muM).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15223330,

title = {Crystal structure of the Drosophila peptidoglycan recognition protein (PGRP)-SA at 1.56 A resolution},

author = {Jean-Baptiste Reiser and Luc Teyton and Ian A Wilson},

doi = {10.1016/j.jmb.2004.04.077},

issn = {0022-2836},

year  = {2004},

date = {2004-07-01},

journal = {J Mol Biol},

volume = {340},

number = {4},

pages = {909--917},

abstract = {Peptidoglycan recognition proteins (PGRPs) form a recently discovered protein family, which is conserved from insect to mammals and is implicated in the innate immune system by interacting with/or degrading microbial peptidoglycans (PGNs). Drosophila PGRP-SA is a member of this family of pattern recognition receptors and is involved in insect Toll activation. We report here the crystal structure of PGRP-SA at 1.56 A resolution, which represents the first example of a "recognition" PGRP. Comparison with the catalytic Drosophila PGRP-LB reveals an overall structure conservation with an L-shaped hydrophilic groove that is likely the PGN carbohydrate core binding site, but further suggests some possible functional homology between recognition and catalytic PGRPs. Consistent with sequence analysis, PGRP-SA does not contain the canonical zinc-binding residues found in catalytic PGRPs. However, substitution of the zinc-binding cysteine residue by serine, along with an altered coordinating histidine residue, assembles a constellation of residues that resembles a modified catalytic triad. The serine/histidine juxtaposition to a threonine residue and a carbonyl oxygen atom, along with conservation of the catalytic water molecule found in PGRP-LB, tantalizingly suggests some hydrolytic function for this member of receptor PGRPs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15162496,

title = {Crystal structure of a glycerophosphodiester phosphodiesterase (GDPD) from Thermotoga maritima (TM1621) at 1.60 A resolution},

author = {Eugenio Santelli and Robert Schwarzenbacher and Daniel McMullan and Tanya Biorac and Linda S Brinen and Jaume M Canaves and Jamison Cambell and Xiaoping Dai and Ashley M Deacon and Marc-André Elsliger and Said Eshagi and Ross Floyd and Adam Godzik and Carina Grittini and Slawomir K Grzechnik and Lukasz Jaroszewski and Cathy Karlak and Heath E Klock and Eric Koesema and John S Kovarik and Andreas Kreusch and Peter Kuhn and Scott A Lesley and Timothy M McPhillips and Mitchell D Miller and Andrew Morse and Kin Moy and Jie Ouyang and Rebecca Page and Kevin Quijano and Fred Rezezadeh and Alyssa Robb and Eric Sims and Glen Spraggon and Raymond C Stevens and Henry van den Bedem and Jeff Velasquez and Juli Vincent and Frank von Delft and Xianhong Wang and Bill West and Guenter Wolf and Qingping Xu and Keith O Hodgson and John Wooley and Ian A Wilson},

doi = {10.1002/prot.20120},

issn = {1097-0134},

year  = {2004},

date = {2004-07-01},

journal = {Proteins},

volume = {56},

number = {1},

pages = {167--170},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15162497,

title = {Crystal structure of a ribose-5-phosphate isomerase RpiB (TM1080) from Thermotoga maritima at 1.90 A resolution},

author = {Qingping Xu and Robert Schwarzenbacher and Daniel McMullan and Frank von Delft and Linda S Brinen and Jaume M Canaves and Xiaoping Dai and Ashley M Deacon and Marc-André Elsliger and Said Eshagi and Ross Floyd and Adam Godzik and Carina Grittini and Slawomir K Grzechnik and Lukasz Jaroszewski and Cathy Karlak and Heath E Klock and Eric Koesema and John S Kovarik and Andreas Kreusch and Peter Kuhn and Scott A Lesley and Inna Levin and Timothy M McPhillips and Mitchell D Miller and Andrew Morse and Kin Moy and Jie Ouyang and Rebecca Page and Kevin Quijano and Alyssa Robb and Glen Spraggon and Raymond C Stevens and Henry van den Bedem and Jeff Velasquez and Juli Vincent and Xianhong Wang and Bill West and Guenter Wolf and Keith O Hodgson and John Wooley and Ian A Wilson},

doi = {10.1002/prot.20129},

issn = {1097-0134},

year  = {2004},

date = {2004-07-01},

journal = {Proteins},

volume = {56},

number = {1},

pages = {171--175},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15209502,

title = {Crystallographic and biochemical analysis of cocaine-degrading antibody 15A10},

author = {N A Larsen and P de Prada and S-X Deng and A Mittal and M Braskett and X Zhu and I A Wilson and D W Landry},

doi = {10.1021/bi049495l},

issn = {0006-2960},

year  = {2004},

date = {2004-06-01},

journal = {Biochemistry},

volume = {43},

number = {25},

pages = {8067--8076},

abstract = {Catalytic antibody 15A10 hydrolyzes the benzoyl ester of cocaine to form the nonpsychoactive metabolites benzoic acid and ecgonine methylester. Here, we report biochemical and structural studies that characterize the catalytic mechanism. The crystal structure of the cocaine-hydrolyzing monoclonal antibody (mAb) 15A10 has been determined at 2.35 A resolution. The binding pocket is fairly shallow and mainly hydrophobic but with a cluster of three hydrogen-bond donating residues (TrpL96, AsnH33, and TyrH35). Computational docking of the transition state analogue (TSA) indicates that these residues are appropriately positioned to coordinate the phosphonate moiety of the TSA and, hence, form an oxyanion hole. Tyrosine modification of the antibody with tetranitromethane reduced hydrolytic activity to background level. The contribution from these and other residues to catalysis and TSA binding was explored by site-directed mutagenesis of 15A10 expressed in a single chain fragment variable (scFv) format. The TyrH35Phe mutant had 4-fold reduced activity, and TrpL96Ala, TrpL96His, and AsnH33Ala mutants were all inactive. Comparison with an esterolytic antibody D2.3 revealed a similar arrangement of tryptophan, asparagine, and tyrosine residues in the oxyanion hole that stabilizes the transition state for ester hydrolysis. Furthermore, the crystal structure of the bacterial cocaine esterase (cocE) also showed that the cocE employs a tyrosine hydroxyl in the oxyanion hole. Thus, the biochemical and structural data are consistent with the catalytic antibody providing oxyanion stabilization as its major contribution to catalysis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15146505,

title = {Crystal structure of an Udp-n-acetylmuramate-alanine ligase MurC (TM0231) from Thermotoga maritima at 2.3 A resolution},

author = {Glen Spraggon and Robert Schwarzenbacher and Andreas Kreusch and Christian C Lee and Polat Abdubek and Eileen Ambing and Tanya Biorac and Linda S Brinen and Jaume M Canaves and Jamison Cambell and Hsiu-Ju Chiu and Xiaoping Dai and Ashley M Deacon and Mike DiDonato and Marc-André Elsliger and Said Eshagi and Ross Floyd and Adam Godzik and Carina Grittini and Slawomir K Grzechnik and Eric Hampton and Lukasz Jaroszewski and Cathy Karlak and Heath E Klock and Eric Koesema and John S Kovarik and Peter Kuhn and Inna Levin and Daniel McMullan and Timothy M McPhillips and Mitchell D Miller and Andrew Morse and Kin Moy and Jie Ouyang and Rebecca Page and Kevin Quijano and Alyssa Robb and Raymond C Stevens and Henry van den Bedem and Jeff Velasquez and Juli Vincent and Frank von Delft and Xianhong Wang and Bill West and Guenter Wolf and Qingping Xu and Keith O Hodgson and John Wooley and Scott A Lesley and Ian A Wilson},

doi = {10.1002/prot.20034},

issn = {1097-0134},

year  = {2004},

date = {2004-06-01},

journal = {Proteins},

volume = {55},

number = {4},

pages = {1078--1081},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15147907,

title = {Monoglucosylated glycans in the secreted human complement component C3: implications for protein biosynthesis and structure},

author = {M D Max Crispin and Gayle E Ritchie and Alison J Critchley and B Paul Morgan and Ian A Wilson and Raymond A Dwek and Robert B Sim and Pauline M Rudd},

doi = {10.1016/j.febslet.2004.04.045},

issn = {0014-5793},

year  = {2004},

date = {2004-05-01},

journal = {FEBS Lett},

volume = {566},

number = {1-3},

pages = {270--274},

abstract = {The monoglucosylated oligomannose N-linked oligosaccharide (Glc(1)Man(9)GlcNAc(2)) is a retention signal for the calnexin-calreticulin quality control pathway in the endoplasmic reticulum. We report here the presence of such monoglucosylated N-glycans on the human complement serum glycoprotein C3. This finding represents the first report of monoglucosylated glycans on a human serum glycoprotein from non-diseased individuals. The presence of the glucose moiety in 5% of the human C3 glycoprotein suggests that this glycosylation site is sequestered within the protein and is consistent with previous studies identifying a cryptic conglutinin binding site on C3 that becomes exposed upon its conversion to iC3b.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15103640,

title = {Crystal structure of a type II quinolic acid phosphoribosyltransferase (TM1645) from Thermotoga maritima at 2.50 A resolution},

author = {Robert Schwarzenbacher and Lukasz Jaroszewski and Frank von Delft and Polat Abdubek and Eileen Ambing and Tanja Biorac and Linda S Brinen and Jaume M Canaves and Jamison Cambell and Hsiu-Ju Chiu and Xiaoping Dai and Ashley M Deacon and Mike DiDonato and Marc-André Elsliger and Said Eshagi and Ross Floyd and Adam Godzik and Carina Grittini and Slawomir K Grzechnik and Eric Hampton and Cathy Karlak and Heath E Klock and Eric Koesema and John S Kovarik and Andreas Kreusch and Peter Kuhn and Scott A Lesley and Inna Levin and Daniel McMullan and Timothy M McPhillips and Mitchell D Miller and Andrew Morse and Kin Moy and Jie Ouyang and Rebecca Page and Kevin Quijano and Alyssa Robb and Glen Spraggon and Raymond C Stevens and Henry van den Bedem and Jeff Velasquez and Juli Vincent and Xianhong Wang and Bill West and Guenter Wolf and Qingping Xu and Keith O Hodgson and John Wooley and Ian A Wilson},

doi = {10.1002/prot.20029},

issn = {1097-0134},

year  = {2004},

date = {2004-05-01},

journal = {Proteins},

volume = {55},

number = {3},

pages = {768--771},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15103638,

title = {Crystal structure of an aspartate aminotransferase (TM1255) from Thermotoga maritima at 1.90 A resolution},

author = {Robert Schwarzenbacher and Lukasz Jaroszewski and Frank von Delft and Polat Abdubek and Eileen Ambing and Tanja Biorac and Linda S Brinen and Jaume M Canaves and Jamison Cambell and Hsui-Ju Chiu and Xiaoping Dai and Ashley M Deacon and Mike DiDonato and Marc-André Elsliger and Said Eshagi and Ross Floyd and Adam Godzik and Carina Grittini and Slawomir K Grzechnik and Eric Hampton and Cathy Karlak and Heath E Klock and Eric Koesema and John S Kovarik and Andreas Kreusch and Peter Kuhn and Scott A Lesley and Inna Levin and Daniel McMullan and Timothy M McPhillips and Mitchell D Miller and Andrew Morse and Kin Moy and Jie Ouyang and Rebecca Page and Kevin Quijano and Alyssa Robb and Glen Spraggon and Raymond C Stevens and Henry van den Bedem and Jeff Velasquez and Juli Vincent and Xianhong Wang and Bill West and Guenter Wolf and Qingping Xu and Keith O Hodgson and John Wooley and Ian A Wilson},

doi = {10.1002/prot.10646},

issn = {1097-0134},

year  = {2004},

date = {2004-05-01},

journal = {Proteins},

volume = {55},

number = {3},

pages = {759--763},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15048837,

title = {Crystal structure of a phosphoribosylaminoimidazole mutase PurE (TM0446) from Thermotoga maritima at 1.77-A resolution},

author = {Robert Schwarzenbacher and Lukasz Jaroszewski and Frank von Delft and Polat Abdubek and Eileen Ambing and Tanya Biorac and Linda S Brinen and Jaume M Canaves and Jamison Cambell and Hsiu-Ju Chiu and Xiaoping Dai and Ashley M Deacon and Mike DiDonato and Marc-André Elsliger and Said Eshagi and Ross Floyd and Adam Godzik and Carina Grittini and Slawomir K Grzechnik and Eric Hampton and Cathy Karlak and Heath E Klock and Eric Koesema and John S Kovarik and Andreas Kreusch and Peter Kuhn and Scott A Lesley and Inna Levin and Daniel McMullan and Timothy M McPhillips and Mitchell D Miller and Andrew Morse and Kin Moy and Jie Ouyang and Rebecca Page and Kevin Quijano and Alyssa Robb and Glen Spraggon and Raymond C Stevens and Henry van den Bedem and Jeff Velasquez and Juli Vincent and Xianhong Wang and Bill West and Guenter Wolf and Qingping Xu and Keith O Hodgson and John Wooley and Ian A Wilson},

doi = {10.1002/prot.20023},

issn = {1097-0134},

year  = {2004},

date = {2004-05-01},

journal = {Proteins},

volume = {55},

number = {2},

pages = {474--478},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14966129,

title = {Crystal structures of human bifunctional enzyme aminoimidazole-4-carboxamide ribonucleotide transformylase/IMP cyclohydrolase in complex with potent sulfonyl-containing antifolates},

author = {Cheom-Gil Cheong and Dennis W Wolan and Samantha E Greasley and Patricia A Horton and G Peter Beardsley and Ian A Wilson},

doi = {10.1074/jbc.M313691200},

issn = {0021-9258},

year  = {2004},

date = {2004-04-01},

journal = {J Biol Chem},

volume = {279},

number = {17},

pages = {18034--18045},

abstract = {Aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/IMP cyclohydrolase (ATIC) is a bifunctional enzyme with folate-dependent AICAR transformylase and IMP cyclohydrolase activities that catalyzes the last two steps of purine biosynthesis. The AICAR transformylase inhibitors BW1540 and BW2315 are sulfamido-bridged 5,8-dideazafolate analogs with remarkably potent K(i) values of 8 and 6 nm, respectively, compared with most other antifolates. Crystal structures of ATIC at 2.55 and 2.60 A with each inhibitor, in the presence of substrate AICAR, revealed that the sulfonyl groups dominate inhibitor binding and orientation through interaction with the proposed oxyanion hole. These agents then appear to mimic the anionic transition state and now implicate Asn(431') in the reaction mechanism along with previously identified key catalytic residues Lys(266) and His(267). Potent and selective inhibition of the AICAR transformylase active site, compared with other folate-dependent enzymes, should therefore be pursued by further design of sulfonyl-containing antifolates.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15084288,

title = {Supine orientation of a murine MHC class I molecule on the membrane bilayer},

author = {Alok K Mitra and Hervé Célia and Gang Ren and John G Luz and Ian A Wilson and Luc Teyton},

doi = {10.1016/j.cub.2004.04.004},

issn = {0960-9822},

year  = {2004},

date = {2004-04-01},

journal = {Curr Biol},

volume = {14},

number = {8},

pages = {718--724},

abstract = {Structural studies of cellular immune receptors such as MHC molecules, T cell receptors (TCR), and TCR/MHC complexes have been carried out with recombinant, soluble forms of the extracytoplasmic domain of these glycoproteins. The important role of the membrane bilayer in T cell recognition and antigen presentation has become increasingly obvious with the description of lipid microdomains. These rafts appear to regulate recognition and signaling by clustering receptors and facilitating the formation of the immune synapse. However, the interactions and orientation of these receptors at the lipid bilayer are unknown. We have used H-2K(b), a major-histocompatibility (MHC) class I molecule, and tethered its soluble domain to a lipid bilayer via a surrogate connecting peptide to reveal the disposition of MHC molecule on the membrane surface. We demonstrate that the long axis of the MHC molecule is approximately parallel to the plane of the membrane with the peptide binding pocket close to the membrane surface. This result was determined by analyzing 4.5A resolution electron crystallographic projection data from frozen-hydrated 2-dimensional crystals. Ionic interactions between the lipid headgroup and the protein appear to be responsible for this orientation, which could establish a "fourth dimension" during MHC/T cell receptor interactions critical for activation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15039553,

title = {Combined pseudo-merohedral twinning, non-crystallographic symmetry and pseudo-translation in a monoclinic crystal form of the gammadelta T-cell ligand T10},

author = {Markus G Rudolph and Christer Wingren and Michael P Crowley and Yueh Hsiu Chien and Ian A Wilson},

doi = {10.1107/S0907444904002239},

issn = {0907-4449},

year  = {2004},

date = {2004-04-01},

journal = {Acta Crystallogr D Biol Crystallogr},

volume = {60},

number = {Pt 4},

pages = {656--664},

abstract = {T10 is a non-classical class Ib-like major histocompatibility complex (MHC) cell-surface antigen which binds directly to certain gammadelta T-cell receptors in the absence of any exogenous and endogenous ligands, such as peculiar lipids or glycolipids. The crystal structure at 2.5 A resolution of murine T10 was determined by molecular replacement using data from an almost perfectly twinned monoclinic crystal. The space group is P2(1), with unit-cell parameters a = 78.2, b = 70.0, c = 139.2 A, beta = 106.8 degrees. Self-rotation function analysis and various intensity statistics revealed the presence of pseudo-merohedral twinning, but these tests underestimated the true twin fraction of alpha approximately 0.46. Native Patterson analyses pointed to the presence of pseudo-translation among the four molecules present in the asymmetric unit. Data analysis, structure determination and model refinement are discussed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14764887,

title = {Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus},

author = {James Stevens and Adam L Corper and Christopher F Basler and Jeffery K Taubenberger and Peter Palese and Ian A Wilson},

doi = {10.1126/science.1093373},

issn = {1095-9203},

year  = {2004},

date = {2004-03-01},

journal = {Science},

volume = {303},

number = {5665},

pages = {1866--1870},

abstract = {The 1918 "Spanish" influenza pandemic represents the largest recorded outbreak of any infectious disease. The crystal structure of the uncleaved precursor of the major surface antigen of the extinct 1918 virus was determined at 3.0 angstrom resolution after reassembly of the hemagglutinin gene from viral RNA fragments preserved in 1918 formalin-fixed lung tissues. A narrow avian-like receptor-binding site, two previously unobserved histidine patches, and a less exposed surface loop at the cleavage site that activates viral membrane fusion reveal structural features primarily found in avian viruses, which may have contributed to the extraordinarily high infectivity and mortality rates observed during 1918.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14997577,

title = {Crystal structure of a putative glutamine amido transferase (TM1158) from Thermotoga maritima at 1.7 A resolution},

author = {Robert Schwarzenbacher and Ashley M Deacon and Lukasz Jaroszewski and Linda S Brinen and Jaume M Canaves and Xiaoping Dai and Marc-André Elsliger and Ross Floyd and Adam Godzik and Carina Grittini and Slawomir K Grzechnik and Heath E Klock and Eric Koesema and John S Kovarik and Andreas Kreusch and Peter Kuhn and Scott A Lesley and Daniel McMullan and Timothy M McPhillips and Mitchell D Miller and Andrew Morse and Kin Moy and Michael S Nelson and Jie Ouyang and Rebecca Page and Alyssa Robb and Kevin Quijano and Glen Spraggon and Raymond C Stevens and Henry van den Bedem and Jeff Velasquez and Juli Vincent and Frank von Delft and Xianhong Wang and Bill West and Guenter Wolf and Keith O Hodgson and John Wooley and Ian A Wilson},

doi = {10.1002/prot.10614},

issn = {1097-0134},

year  = {2004},

date = {2004-03-01},

journal = {Proteins},

volume = {54},

number = {4},

pages = {801--805},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14997578,

title = {Crystal structure of an HEPN domain protein (TM0613) from Thermotoga maritima at 1.75 A resolution},

author = {Heidi Erlandsen and Jaume M Canaves and Marc-André Elsliger and Frank von Delft and Linda S Brinen and Xiaoping Dai and Ashley M Deacon and Ross Floyd and Adam Godzik and Carina Grittini and Slawomir K Grzechnik and Lukasz Jaroszewski and Heath E Klock and Eric Koesema and John S Kovarik and Andreas Kreusch and Peter Kuhn and Scott A Lesley and Daniel McMullan and Timothy M McPhillips and Mitchell D Miller and Andrew Morse and Kin Moy and Jie Ouyang and Rebecca Page and Alyssa Robb and Kevin Quijano and Robert Schwarzenbacher and Glen Spraggon and Raymond C Stevens and Henry van den Bedem and Jeff Velasquez and Juli Vincent and Xianhong Wang and Bill West and Guenter Wolf and Keith O Hodgson and John Wooley and Ian A Wilson},

doi = {10.1002/prot.10631},

issn = {1097-0134},

year  = {2004},

date = {2004-03-01},

journal = {Proteins},

volume = {54},

number = {4},

pages = {806--809},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14978103,

title = {A peptide that antagonizes TCR-mediated reactions with both syngeneic and allogeneic agonists: functional and structural aspects},

author = {Markus G Rudolph and Lucy Q Shen and Stephen A Lamontagne and John G Luz and Joseph R Delaney and Qing Ge and Bryan K Cho and Deborah Palliser and Carol A McKinley and Jianzhu Chen and Ian A Wilson and Herman N Eisen},

doi = {10.4049/jimmunol.172.5.2994},

issn = {0022-1767},

year  = {2004},

date = {2004-03-01},

journal = {J Immunol},

volume = {172},

number = {5},

pages = {2994--3002},

abstract = {We identify and consider some characteristics of a peptide antagonist for the Ag-specific receptor on 2C cells (the 2C TCR). The peptide, GNYSFYAL (called GNY), binds to H-2K(b), and a very high-resolution crystal structure of the GNY-K(b) complex at 1.35 A is described. Although the GNY peptide does not bind to L(d), the potency of GNY-K(b) as an antagonist is evident from its ability to specifically inhibit 2C TCR-mediated reactions to an allogenic agonist complex (QLSPFPFDL-L(d)), as well as to a syngeneic agonist complex (SIYRYYGL-K(b)). The crystal structure and the activities of alanine-substituted peptide variants point to the properties of the peptide P4 side chain and the conformation of the Tyr-P6 side chain as the structural determinants of GNYSFYAL antagonist activity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14990699,

title = {Genetic and phenotypic analyses of human immunodeficiency virus type 1 escape from a small-molecule CCR5 inhibitor},

author = {Shawn E Kuhmann and Pavel Pugach and Kevin J Kunstman and Joann Taylor and Robyn L Stanfield and Amy Snyder and Julie M Strizki and Janice Riley and Bahige M Baroudy and Ian A Wilson and Bette T Korber and Steven M Wolinsky and John P Moore},

doi = {10.1128/jvi.78.6.2790-2807.2004},

issn = {0022-538X},

year  = {2004},

date = {2004-03-01},

journal = {J Virol},

volume = {78},

number = {6},

pages = {2790--2807},

abstract = {We have described previously the generation of an escape variant of human immunodeficiency virus type 1 (HIV-1), under the selection pressure of AD101, a small molecule inhibitor that binds the CCR5 coreceptor (A. Trkola, S. E. Kuhmann, J. M. Strizki, E. Maxwell, T. Ketas, T. Morgan, P. Pugach, S. X. L. Wojcik, J. Tagat, A. Palani, S. Shapiro, J. W. Clader, S. McCombie, G. R. Reyes, B. M. Baroudy, and J. P. Moore, Proc. Natl. Acad. Sci. USA 99:395-400, 2002). The escape mutant, CC101.19, continued to use CCR5 for entry, but it was at least 20,000-fold more resistant to AD101 than the parental virus, CC1/85. We have now cloned the env genes from the the parental and escape mutant isolates and made chimeric infectious molecular clones that fully recapitulate the phenotypes of the corresponding isolates. Sequence analysis of the evolution of the escape mutants suggested that the most relevant changes were likely to be in the V3 loop of the gp120 glycoprotein. We therefore made a series of mutant viruses and found that full AD101 resistance was conferred by four amino acid changes in V3. Each change individually caused partial resistance when they were introduced into the V3 loop of a CC1/85 clone, but their impact was dependent on the gp120 context in which they were made. We assume that these amino acid changes alter how the HIV-1 Env complex interacts with CCR5. Perhaps unexpectedly, given the complete dependence of the escape mutant on CCR5 for entry, monomeric gp120 proteins expressed from clones of the fully resistant isolate failed to bind to CCR5 on the surface of L1.2-CCR5 cells under conditions where gp120 proteins from the parental virus and a partially AD101-resistant virus bound strongly. Hence, the full impact of the V3 substitutions may only be apparent at the level of the native Env complex.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14985706,

title = {HIV vaccine design and the neutralizing antibody problem},

author = {Dennis R Burton and Ronald C Desrosiers and Robert W Doms and Wayne C Koff and Peter D Kwong and John P Moore and Gary J Nabel and Joseph Sodroski and Ian A Wilson and Richard T Wyatt},

doi = {10.1038/ni0304-233},

issn = {1529-2908},

year  = {2004},

date = {2004-03-01},

journal = {Nat Immunol},

volume = {5},

number = {3},

pages = {233--236},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14990736,

title = {The long third complementarity-determining region of the heavy chain is important in the activity of the broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2F5},

author = {Michael B Zwick and H Kiyomi Komori and Robyn L Stanfield and Sarah Church and Meng Wang and Paul W H I Parren and Renate Kunert and Hermann Katinger and Ian A Wilson and Dennis R Burton},

doi = {10.1128/jvi.78.6.3155-3161.2004},

issn = {0022-538X},

year  = {2004},

date = {2004-03-01},

journal = {J Virol},

volume = {78},

number = {6},

pages = {3155--3161},

abstract = {The human monoclonal antibody 2F5 neutralizes primary human immunodeficiency virus type 1 (HIV-1) with rare breadth and potency. A crystal structure of a complex of 2F5 and a peptide corresponding to its core epitope on gp41, ELDKWAS, revealed that the peptide interacts with residues at the base of the unusually long (22-residue) third complementarity-determining region of the heavy chain (CDR H3) but not the apex. Here, we perform alanine-scanning mutagenesis across CDR H3 and make additional substitutions of selected residues to map the paratope of Fab 2F5. Substitution of residues from the base of the H3 loop or from CDRs H1, H2, and L3, which are proximal to the peptide, significantly diminished the affinity of Fab 2F5 for gp41 and a short peptide containing the 2F5 core motif. However, nonconservative substitutions to a phenylalanine residue at the apex of the H3 loop also markedly decreased 2F5 binding to both gp41 and the peptide, suggesting that recognition of the core epitope is crucially dependent on features at the apex of the H3 loop. Furthermore, substitution at the apex of the H3 loop had an even more pronounced effect on the neutralizing activity of 2F5 against three sensitive HIV-1. These observations present a challenge to vaccine strategies based on peptide mimics of the linear epitope.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14997579,

title = {Crystal structure of a putative PII-like signaling protein (TM0021) from Thermotoga maritima at 2.5 A resolution},

author = {Robert Schwarzenbacher and Frank von Delft and Polat Abdubek and Eileen Ambing and Tanja Biorac and Linda S Brinen and Jaume M Canaves and Jamison Cambell and Hsui-Ju Chiu and Xiaoping Dai and Ashley M Deacon and Mike DiDonato and Marc-André Elsliger and Said Eshagi and Ross Floyd and Adam Godzik and Carina Grittini and Slawomir K Grzechnik and Eric Hampton and Lukasz Jaroszewski and Cathy Karlak and Heath E Klock and Eric Koesema and John S Kovarik and Andreas Kreusch and Peter Kuhn and Scott A Lesley and Inna Levin and Daniel McMullan and Timothy M McPhillips and Mitchell D Miller and Andrew Morse and Kin Moy and Jie Ouyang and Rebecca Page and Kevin Quijano and Alyssa Robb and Glen Spraggon and Raymond C Stevens and Henry van den Bedem and Jeff Velasquez and Juli Vincent and Xianhong Wang and Bill West and Guenter Wolf and Qingping Xu and Keith O Hodgson and John Wooley and Ian A Wilson},

doi = {10.1002/prot.10647},

issn = {1097-0134},

year  = {2004},

date = {2004-03-01},

journal = {Proteins},

volume = {54},

number = {4},

pages = {810--813},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14982995,

title = {Probing the antibody-catalyzed water-oxidation pathway at atomic resolution},

author = {Xueyong Zhu and Paul Wentworth and Anita D Wentworth and Albert Eschenmoser and Richard A Lerner and Ian A Wilson},

doi = {10.1073/pnas.0307311101},

issn = {0027-8424},

year  = {2004},

date = {2004-02-01},

journal = {Proc Natl Acad Sci U S A},

volume = {101},

number = {8},

pages = {2247--2252},

abstract = {Antibodies can catalyze the generation of hydrogen peroxide (H2O2) from singlet dioxygen (1O2*) and water via the postulated intermediacy of dihydrogen trioxide (H2O3) and other trioxygen species. Nine different crystal structures were determined to elucidate the chemical consequences to the antibody molecule itself of exposure to such reactive intermediates and to provide insights into the location on the antibody where these species could be generated. Herein, we report structural evidence for modifications of two specific antibody residues within the interfacial region of the variable and constant domains of different murine antibody antigen-binding fragments (Fabs) by reactive species generated during the antibody-catalyzed water oxidation process. Crystal structure analyses of murine Fabs 4C6 and 13G5 after UV-irradiation revealed complex oxidative modifications to tryptophan L163 and, in 4C6, hydroxylation of the Cgamma of glutamine H6. These discrete modifications of specific residues add further support for the "active site" of the water-oxidation pathway being located within the interfacial region of the constant and variable domains and highlight the general resistance of the antibody molecule to oxidation by reactive oxygen species generated during the water-oxidation process.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14966891,

title = {Reactivity-based one-pot synthesis of oligomannoses: defining antigens recognized by 2G12, a broadly neutralizing anti-HIV-1 antibody},

author = {Hing-Ken Lee and Christopher N Scanlan and Cheng-Yuan Huang and Aileen Y Chang and Daniel A Calarese and Raymond A Dwek and Pauline M Rudd and Dennis R Burton and Ian A Wilson and Chi-Huey Wong},

doi = {10.1002/anie.200353105},

issn = {1433-7851},

year  = {2004},

date = {2004-02-01},

journal = {Angew Chem Int Ed Engl},

volume = {43},

number = {8},

pages = {1000--1003},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14756553,

title = {Structural insights into the human and avian IMP cyclohydrolase mechanism via crystal structures with the bound XMP inhibitor},

author = {Dennis W Wolan and Cheom-Gil Cheong and Samantha E Greasley and Ian A Wilson},

doi = {10.1021/bi030162i},

issn = {0006-2960},

year  = {2004},

date = {2004-02-01},

journal = {Biochemistry},

volume = {43},

number = {5},

pages = {1171--1183},

abstract = {Within de novo purine biosynthesis, the AICAR transformylase and IMP cyclohydrolase activities of the bifunctional enzyme ATIC convert the intermediate AICAR to the final product of the pathway, IMP. Identification of the AICAR transformylase active site and a proposed formyl transfer mechanism have already resulted from analysis of crystal structures of avian ATIC in complex with substrate and/or inhibitors. Herein, we focus on the IMPCH active site and the cyclohydrolase mechanism through comparison of crystal structures of XMP inhibitor complexes of human ATIC at 1.9 A resolution with the previously determined avian enzyme. This first human ATIC structure was also determined to ascertain whether any subtle structural differences, compared to the homologous avian enzyme, should be taken into account for structure-based inhibitor design. These structural comparisons, as well as comparative analyses with other IMP and XMP binding proteins, have enabled a catalytic mechanism to be formulated. The primary role of the IMPCH active site appears to be to induce a reconfiguration of the substrate FAICAR to a less energetically favorable, but more reactive, conformer. Backbone (Arg64 and Lys66) and side chain interactions (Thr67) in the IMPCH active site reorient the 4-carboxamide from the preferred conformer that binds to the AICAR Tfase active site to one that promotes intramolecular cyclization. Other backbone amides (Ile126 and Gly127) create an oxyanion hole that helps orient the formyl group for nucleophilic attack by the 4-carboxamide amine and then stabilize the anionic intermediate. Several other residues, including Lys66, Tyr104, Asp125, and Lys137', provide substrate specificity and likely enhance the catalytic rate through contributions to acid-base catalysis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14962380,

title = {Structural rationale for the broad neutralization of HIV-1 by human monoclonal antibody 447-52D},

author = {Robyn L Stanfield and Miroslaw K Gorny and Constance Williams and Susan Zolla-Pazner and Ian A Wilson},

doi = {10.1016/j.str.2004.01.003},

issn = {0969-2126},

year  = {2004},

date = {2004-02-01},

journal = {Structure},

volume = {12},

number = {2},

pages = {193--204},

abstract = {447-52D is a human monoclonal antibody isolated from a heterohybridoma derived from an HIV-1-infected individual. This antibody recognizes the hypervariable gp120 V3 loop, and neutralizes both X4 and R5 primary isolates, making it one of the most effective anti-V3 antibodies characterized to date. The crystal structure of the 447-52D Fab in complex with a 16-mer V3 peptide at 2.5 A resolution reveals that the peptide beta hairpin forms a three-stranded mixed beta sheet with complementarity determining region (CDR) H3, with most of the V3 side chains exposed to solvent. Sequence specificity is conferred through interaction of the type-II turn (residues GPGR) at the apex of the V3 hairpin with the base of CDR H3. This novel mode of peptide-antibody recognition enables the antibody to bind to many different V3 sequences where only the GPxR core epitope is absolutely required.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14739458,

title = {T cell activation by lipopeptide antigens},

author = {D Branch Moody and David C Young and Tan-Yun Cheng and Jean-Pierre Rosat and Carme Roura-Mir and Peter B O'Connor and Dirk M Zajonc and Andrew Walz and Marvin J Miller and Steven B Levery and Ian A Wilson and Catherine E Costello and Michael B Brenner},

doi = {10.1126/science.1089353},

issn = {1095-9203},

year  = {2004},

date = {2004-01-01},

journal = {Science},

volume = {303},

number = {5657},

pages = {527--531},

abstract = {Unlike major histocompatibility proteins, which bind peptides, CD1 proteins display lipid antigens to T cells. Here, we report that CD1a presents a family of previously unknown lipopeptides from Mycobacterium tuberculosis, named didehydroxymycobactins because of their structural relation to mycobactin siderophores. T cell activation was mediated by the alphabeta T cell receptors and was specific for structure of the acyl and peptidic components of these antigens. These studies identify a means of intracellular pathogen detection and identify lipopeptides as a biochemical class of antigens for T cells, which, like conventional peptides, have a potential for marked structural diversity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14715906,

title = {Rapid refinement of crystallographic protein construct definition employing enhanced hydrogen/deuterium exchange MS},

author = {Dennis Pantazatos and Jack S Kim and Heath E Klock and Raymond C Stevens and Ian A Wilson and Scott A Lesley and Virgil L Woods},

doi = {10.1073/pnas.0307204101},

issn = {0027-8424},

year  = {2004},

date = {2004-01-01},

journal = {Proc Natl Acad Sci U S A},

volume = {101},

number = {3},

pages = {751--756},

abstract = {Crystallographic efforts often fail to produce suitably diffracting protein crystals. Unstructured regions of proteins play an important role in this problem and considerable advantage can be gained in removing them. We have developed a number of enhancements to amide hydrogen/high-throughput and high-resolution deuterium exchange MS (DXMS) technology that allow rapid identification of unstructured regions in proteins. To demonstrate the utility of this approach for improving crystallization success, DXMS analysis was attempted on 24 Thermotoga maritima proteins with varying crystallization and diffraction characteristics. Data acquisition and analysis for 21 of these proteins was completed in 2 weeks and resulted in the localization and prediction of several unstructured regions within the proteins. When compared with those targets of known structure, the DXMS method correctly localized even small regions of disorder. DXMS analysis was then correlated with the propensity of such targets to crystallize and was further used to define truncations that improved crystallization. Truncations that were defined solely on DXMS analysis demonstrated greatly improved crystallization and have been used for structure determination. This approach represents a rapid and generalized method that can be applied to structural genomics or other targets in a high-throughput manner.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14705036,

title = {Crystal structure of an iron-containing 1,3-propanediol dehydrogenase (TM0920) from Thermotoga maritima at 1.3 A resolution},

author = {Robert Schwarzenbacher and Frank von Delft and Jaume M Canaves and Linda S Brinen and Xiaoping Dai and Ashley M Deacon and Marc A Elsliger and Said Eshaghi and Ross Floyd and Adam Godzik and Carina Grittini and Slawomir K Grzechnik and Chittibabu Guda and Lukasz Jaroszewski and Cathy Karlak and Heath E Klock and Eric Koesema and John S Kovarik and Andreas Kreusch and Peter Kuhn and Scott A Lesley and Daniel McMullan and Timothy M McPhillips and Mark A Miller and Mitchell D Miller and Andrew Morse and Kin Moy and Jie Ouyang and Rebecca Page and Alyssa Robb and Kevin Rodrigues and Thomas L Selby and Glen Spraggon and Raymond C Stevens and Henry van den Bedem and Jeff Velasquez and Juli Vincent and Xianhong Wang and Bill West and Guenter Wolf and Keith O Hodgson and John Wooley and Ian A Wilson},

doi = {10.1002/prot.10594},

issn = {1097-0134},

year  = {2004},

date = {2004-01-01},

journal = {Proteins},

volume = {54},

number = {1},

pages = {174--177},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14705032,

title = {Crystal structure of gamma-glutamyl phosphate reductase (TM0293) from Thermotoga maritima at 2.0 A resolution},

author = {Rebecca Page and Michael S Nelson and Frank von Delft and Marc-André Elsliger and Jaume M Canaves and Linda S Brinen and Xiaoping Dai and Ashley M Deacon and Ross Floyd and Adam Godzik and Carina Grittini and Slawomir K Grzechnik and Lukasz Jaroszewski and Heath E Klock and Eric Koesema and John S Kovarik and Andreas Kreusch and Peter Kuhn and Scott A Lesley and Daniel McMullan and Timothy M McPhillips and Mitchell D Miller and Andrew Morse and Kin Moy and Jie Ouyang and Alyssa Robb and Kevin Rodrigues and Robert Schwarzenbacher and Glen Spraggon and Raymond C Stevens and Henry van den Bedem and Jeff Velasquez and Juli Vincent and Xianhong Wang and Bill West and Guenter Wolf and Keith O Hodgson and John Wooley and Ian A Wilson},

doi = {10.1002/prot.10562},

issn = {1097-0134},

year  = {2004},

date = {2004-01-01},

journal = {Proteins},

volume = {54},

number = {1},

pages = {157--161},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14592768,

title = {Recurring conformation of the human immunodeficiency virus type 1 gp120 V3 loop},

author = {Robyn L Stanfield and Jayant B Ghiara and Erica Ollmann Saphire and Albert T Profy and Ian A Wilson},

doi = {10.1016/s0042-6822(03)00525-7},

issn = {0042-6822},

year  = {2003},

date = {2003-10-01},

journal = {Virology},

volume = {315},

number = {1},

pages = {159--173},

abstract = {The crystal structure of the human immunodeficiency virus type 1 (HIV-1) neutralizing, murine Fab 83.1 in complex with an HIV-1 gp120 V3 peptide has been determined to 2.57 A resolution. The conformation of the V3 loop peptide in complex with Fab 83.1 is very similar to V3 conformations seen previously with two other neutralizing Fabs, 50.1 and 59.1. The repeated identification of this same V3 conformation in complex with three very different, neutralizing antibodies indicates that it is a highly preferred structure for V3 loops on some strains of the HIV-1 virus.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12945057,

title = {Crystal structure of uronate isomerase (TM0064) from Thermotoga maritima at 2.85 A resolution},

author = {Robert Schwarzenbacher and Jaume M Canaves and Linda S Brinen and Xiaoping Dai and Ashley M Deacon and Marc A Elsliger and Said Eshaghi and Ross Floyd and Adam Godzik and Carina Grittini and Slawomir K Grzechnik and Chittibabu Guda and Lukasz Jaroszewski and Cathy Karlak and Heath E Klock and Eric Koesema and John S Kovarik and Andreas Kreusch and Peter Kuhn and Scott A Lesley and Daniel McMullan and Timothy M McPhillips and Mark A Miller and Mitchell D Miller and Andrew Morse and Kin Moy and Jie Ouyang and Alyssa Robb and Kevin Rodrigues and Thomas L Selby and Glen Spraggon and Raymond C Stevens and Henry van den Bedem and Jeff Velasquez and Juli Vincent and Xianhong Wang and Bill West and Guenter Wolf and Keith O Hodgson and John Wooley and Ian A Wilson},

doi = {10.1002/prot.10462},

issn = {1097-0134},

year  = {2003},

date = {2003-10-01},

journal = {Proteins},

volume = {53},

number = {1},

pages = {142--145},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid13129587,

title = {Design, synthesis and biological evaluation of 10-CF3CO-DDACTHF analogues and derivatives as inhibitors of GAR Tfase and the de novo purine biosynthetic pathway},

author = {Joel Desharnais and Inkyu Hwang and Yan Zhang and Ali Tavassoli and Justin Baboval and Stephen J Benkovic and Ian A Wilson and Dale L Boger},

doi = {10.1016/s0968-0896(03)00458-9},

issn = {0968-0896},

year  = {2003},

date = {2003-10-01},

journal = {Bioorg Med Chem},

volume = {11},

number = {20},

pages = {4511--4521},

abstract = {The synthesis and evaluation of analogues and key derivatives of 10-CF3CO-DDACTHF as inhibitors of glycinamide ribonucleotide transformylase (GAR Tfase) and aminoimidazole carboxamide transformylase (AICAR Tfase) are reported. Polyglutamate analogues of 1 were evaluated as inhibitors of Escherichia coli and recombinant human (rh) GAR Tfase, and AICAR Tfase. Although the pentaglutamate 6 was found to be the most active inhibitor of the series tested against rhGAR Tfase (Ki=0.004 microM), little distinction between the mono-pentaglutamate derivatives was observed (Ki=0.02-0.004 microM), suggesting that the principal role of the required polyglutamation of 1 is intracellular retention. In contrast, 1 and its defined polyglutamates 3-6 were much less inactive when tested against rhAICAR Tfase (Ki=65-0.120 microM) and very selective (> or =100-fold) for rh versus E. coli GAR Tfase. Additional key analogues of 1 were examined (7 and 8) and found to be much less active (1000-fold) highlighting the exceptional characteristics of 1.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid13129585,

title = {Design, synthesis, and biological evaluation of simplified alpha-keto heterocycle, trifluoromethyl ketone, and formyl substituted folate analogues as potential inhibitors of GAR transformylase and AICAR transformylase},

author = {Thomas H Marsilje and Michael P Hedrick and Joel Desharnais and Ali Tavassoli and Yan Zhang and Ian A Wilson and Stephen J Benkovic and Dale L Boger},

doi = {10.1016/s0968-0896(03)00456-5},

issn = {0968-0896},

year  = {2003},

date = {2003-10-01},

journal = {Bioorg Med Chem},

volume = {11},

number = {20},

pages = {4487--4501},

abstract = {A series of simplified alpha-keto heterocycle, trifluoromethyl ketone, and formyl substituted folate analogues lacking the benzoylglutamate subunit were prepared and examined as potential inhibitors of glycinamide ribonucleotide transformylase (GAR Tfase) and aminoimidazole carboxamide transformylase (AICAR Tfase).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid13129586,

title = {10-(2-benzoxazolcarbonyl)-5,10-dideaza-acyclic-5,6,7,8-tetrahydrofolic acid: a potential inhibitor of GAR transformylase and AICAR transformylase},

author = {Thomas H Marsilje and Michael P Hedrick and Joel Desharnais and Kevin Capps and Ali Tavassoli and Yan Zhang and Ian A Wilson and Stephen J Benkovic and Dale L Boger},

doi = {10.1016/s0968-0896(03)00457-7},

issn = {0968-0896},

year  = {2003},

date = {2003-10-01},

journal = {Bioorg Med Chem},

volume = {11},

number = {20},

pages = {4503--4509},

abstract = {The design and synthesis of 10-(2-benzoxazolcarbonyl)-DDACTHF (1) as an inhibitor of glycinamide ribonucleotide transformylase (GAR Tfase) and aminoimidazole carboxamide transformylase (AICAR Tfase) are reported. Ketone 1 and the corresponding alcohol 13 were evaluated for inhibition of GAR Tfase and AICAR Tfase and the former was found to be a potent inhibitor of recombinant human (rh) GAR Tfase (Ki=600 nM).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12972259,

title = {A humanized aldolase antibody for selective chemotherapy and adaptor immunotherapy},

author = {Christoph Rader and James M Turner and Andreas Heine and Doron Shabat and Subhash C Sinha and Ian A Wilson and Richard A Lerner and Carlos F Barbas},

doi = {10.1016/s0022-2836(03)00992-6},

issn = {0022-2836},

year  = {2003},

date = {2003-09-01},

journal = {J Mol Biol},

volume = {332},

number = {4},

pages = {889--899},

abstract = {Mouse monoclonal antibody 38C2 is the prototype of a new class of catalytic antibodies that were generated by reactive immunization. Through a reactive lysine, 38C2 catalyzes aldol and retro-aldol reactions using the enamine mechanism of natural aldolases. In addition to its remarkable versatility and efficacy in synthetic organic chemistry, 38C2 has been used for the selective activation of prodrugs in vitro and in vivo and thereby emerged as a promising tool for selective chemotherapy. Adding another application with relevance for cancer therapy, designated adaptor immunotherapy, we have recently shown that 38C2 can be chemically programmed to target tumors by formation of a covalent bond of defined stoichiometry with a beta-diketone derivative of an integrin alpha(v)beta(3) targeting RGD peptidomimetic. However, a major limitation for the transition from preclinical to clinical evaluation is the human anti-mouse antibody immune response that mouse 38C2 is likely to elicit in a majority of patients after single administration. Here, we report the humanization of mouse 38C2 based on rational design guided by molecular modeling. In essence, the catalytic center of mouse 38C2, which encompasses a deep hydrophobic pocket with a reactive lysine residue at the bottom, was grafted into a human antibody framework. Humanized 38C2 IgG1 was found to bind to beta-diketone haptens with conserved affinities and revealed strong catalytic activity with identical k(cat) and slightly higher K(M) values compared to the parental mouse antibody. Furthermore, humanized 38C2 IgG1 revealed efficiency in prodrug activation and chemical programming comparable to the parental mouse antibody.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12974624,

title = {Structure of avian AICAR transformylase with a multisubstrate adduct inhibitor beta-DADF identifies the folate binding site},

author = {Dennis W Wolan and Samantha E Greasley and Mark J Wall and Stephen J Benkovic and Ian A Wilson},

doi = {10.1021/bi030106h},

issn = {0006-2960},

year  = {2003},

date = {2003-09-01},

journal = {Biochemistry},

volume = {42},

number = {37},

pages = {10904--10914},

abstract = {The penultimate catalytic step of the purine de novo synthesis pathway is the conversion of aminoimidazole-4-carboxamide ribonucleotide (AICAR) to 5-formyl-AICAR that requires the cofactor N(10)-formyl-tetrahydrofolate as the formyl donor. This reaction is catalyzed by the AICAR transformylase domain of the bifunctional enzyme AICAR transformylase/inosine monophosphate cyclohydrolase (ATIC). Identification of the location of the AICAR transformylase active site was previously elucidated from the crystal structure of the avian ATIC with bound substrate AICAR; however, due to the absence of any bound folate, the folate binding region of the active site could not be identified. Here, we have determined the homodimeric crystal structure of avian ATIC in complex with the ATIC-specific multisubstrate adduct inhibitor beta-DADF to 2.5 A resolution. Beta-DADF encompasses both the AICAR and folate moieties into a single covalently linked entity, thereby allowing for the characterization of the folate binding pocket of the AICAR transformylase active site. Beta-DADF is intimately bound at the dimer interface of the transformylase domains with the majority of AICAR moiety interactions occurring within one subunit, whereas the primary interactions to the folate occur with the opposing subunit. The crystal structure suggests that a buried Lys(267) is transiently protonated during formyl transfer allowing for the stabilization of the oxyanion transition state and subsequent protonation of N10 on the tetrahydrofolate leaving group. Furthermore, the beta-DADF-bound structure provides a more optimal three-dimensional scaffold to improve the design of specific antineoplastic agents.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12833155,

title = {Crystal structure of CD1a in complex with a sulfatide self antigen at a resolution of 2.15 A},

author = {Dirk M Zajonc and Marc A Elsliger and Luc Teyton and Ian A Wilson},

doi = {10.1038/ni948},

issn = {1529-2908},

year  = {2003},

date = {2003-08-01},

journal = {Nat Immunol},

volume = {4},

number = {8},

pages = {808--815},

abstract = {CD1 antigens bind a variety of self and foreign lipid and glycolipid antigens for presentation to CD1-restricted T cell receptors (TCRs). Here we report the crystal structure of human CD1a in complex with a sulfatide self antigen at a resolution of 2.15 A. The lipid adopts an S-shaped conformation, with the sphingosine chain completely buried in the A' pocket and the fatty acid chain emerging from the interface of the A' pocket into the more exposed F' pocket. The headgroup is anchored in the A'-F' junction and protrudes into the F' pocket for TCR recognition. Because the A' pocket is narrow with a fixed terminus, it can act as a molecular 'ruler' to select alkyl chains of a particular length.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12829775,

title = {Antibody domain exchange is an immunological solution to carbohydrate cluster recognition},

author = {Daniel A Calarese and Christopher N Scanlan and Michael B Zwick and Songpon Deechongkit and Yusuke Mimura and Renate Kunert and Ping Zhu and Mark R Wormald and Robyn L Stanfield and Kenneth H Roux and Jeffery W Kelly and Pauline M Rudd and Raymond A Dwek and Hermann Katinger and Dennis R Burton and Ian A Wilson},

doi = {10.1126/science.1083182},

issn = {1095-9203},

year  = {2003},

date = {2003-06-01},

journal = {Science},

volume = {300},

number = {5628},

pages = {2065--2071},

abstract = {Human antibody 2G12 neutralizes a broad range of human immunodeficiency virus type 1 (HIV-1) isolates by binding an unusually dense cluster of carbohydrate moieties on the "silent" face of the gp120 envelope glycoprotein. Crystal structures of Fab 2G12 and its complexes with the disaccharide Manalpha1-2Man and with the oligosaccharide Man9GlcNAc2 revealed that two Fabs assemble into an interlocked VH domain-swapped dimer. Further biochemical, biophysical, and mutagenesis data strongly support a Fab-dimerized antibody as the prevalent form that recognizes gp120. The extraordinary configuration of this antibody provides an extended surface, with newly described binding sites, for multivalent interaction with a conserved cluster of oligomannose type sugars on the surface of gp120. The unique interdigitation of Fab domains within an antibody uncovers a previously unappreciated mechanism for high-affinity recognition of carbohydrate or other repeating epitopes on cell or microbial surfaces.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12652485,

title = {Expression and characterization of a humanized cocaine-binding antibody},

author = {El-Rashdy M Redwan and Nicholas A Larsen and Bin Zhou and Peter Wirsching and Kim D Janda and Ian A Wilson},

doi = {10.1002/bit.10598},

issn = {0006-3592},

year  = {2003},

date = {2003-06-01},

journal = {Biotechnol Bioeng},

volume = {82},

number = {5},

pages = {612--618},

abstract = {The murine immunoglobulin G (IgG) cocaine-binding monoclonal antibody (mAb), GNC92H2, is notable for its exquisite specificity for cocaine, as opposed to chemically-related cocaine metabolites, and for its moderately high affinity (K(d) approximately 200 nM) for cocaine. Recently, we described the crystal structure of a mouse/human chimeric Fab construct at 2.3 A resolution. Herein, we report the successful framework humanization of a single-chain Fv (scFv) GNC92H2 construct without loss of affinity for cocaine. In brief, we compared the mAb GNC92H2 sequence to human antibody sequences, and used structure-based design to incorporate mutations (total = 49) that would humanize the framework region without affecting the overall shape of the binding pocket or the key cocaine-contact residues. The codons of the rationally designed sequence were optimized for E. coli expression, and the gene was synthesized by a de novo PCR reaction using 14 overlapping primers. Expression of the scFv construct was significantly improved in E. coli by fusion to thioredoxin. Intriguingly, this construct apparently refolds to form soluble active antibody in the reducing environment of the cytoplasm. Competitive ELISA and equilibrium dialysis demonstrated comparable binding activity between the humanized scFv and the whole IgG. The successful humanization of mAb GNC92H2 should enhance its potential therapeutic value by reducing its overall. immunogenicity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12637583,

title = {Secretory IgA N- and O-glycans provide a link between the innate and adaptive immune systems},

author = {Louise Royle and Anja Roos and David J Harvey and Mark R Wormald and Daniëlle van Gijlswijk-Janssen and El-Rashdy M Redwan and Ian A Wilson and Mohamed R Daha and Raymond A Dwek and Pauline M Rudd},

doi = {10.1074/jbc.M301436200},

issn = {0021-9258},

year  = {2003},

date = {2003-05-01},

journal = {J Biol Chem},

volume = {278},

number = {22},

pages = {20140--20153},

abstract = {Secretory IgA (SIgA) is a multi-polypeptide complex consisting of a secretory component (SC) covalently attached to dimeric IgA containing one joining (J) chain. We present the analysis of both the N- and O-glycans on the individual peptides from this complex. Based on these data, we have constructed a molecular model of SIgA1 with all its glycans, in which the Fab arms form a T shape and the SC is wrapped around the heavy chains. The O-glycan regions on the heavy (H) chains and the SC N-glycans have adhesin-binding glycan epitopes including galactose-linked beta1-4 and beta1-3 to GlcNAc, fucose-linked alpha1-3 and alpha1-4 to GlcNAc and alpha1-2 to galactose, and alpha2-3 and alpha2-6-linked sialic acids. These glycan epitopes provide SIgA with further bacteria-binding sites in addition to the four Fab-binding sites, thus enabling SIgA to participate in both innate and adaptive immunity. We also show that the N-glycans on the H chains of both SIgA1 and SIgA2 present terminal GlcNAc and mannose residues that are normally masked by SC, but that can be unmasked and recognized by mannose-binding lectin, by disrupting the SC-H chain noncovalent interactions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12755606,

title = {Rational design, synthesis, evaluation, and crystal structure of a potent inhibitor of human GAR Tfase: 10-(trifluoroacetyl)-5,10-dideazaacyclic-5,6,7,8-tetrahydrofolic acid},

author = {Yan Zhang and Joel Desharnais and Thomas H Marsilje and Chenglong Li and Michael P Hedrick and Lata T Gooljarsingh and Ali Tavassoli and Stephen J Benkovic and Arthur J Olson and Dale L Boger and Ian A Wilson},

doi = {10.1021/bi034219c},

issn = {0006-2960},

year  = {2003},

date = {2003-05-01},

journal = {Biochemistry},

volume = {42},

number = {20},

pages = {6043--6056},

abstract = {Glycinamide ribonucleotide transformylase (GAR Tfase) has been the target of anti-neoplastic intervention for almost two decades. Here, we use a structure-based approach to design a novel folate analogue, 10-(trifluoroacetyl)-5,10-dideazaacyclic-5,6,7,8-tetrahydrofolic acid (10-CF(3)CO-DDACTHF, 1), which specifically inhibits recombinant human GAR Tfase (K(i) = 15 nM), but is inactive (K(i) > 100 microM) against other folate-dependent enzymes that have been examined. Moreover, compound 1 is a potent inhibitor of tumor cell proliferation (IC(50) = 16 nM, CCRF-CEM), which represents a 10-fold improvement over Lometrexol, a GAR Tfase inhibitor that has been in clinical trials. Thus, this folate analogue 1 is among the most potent and selective inhibitors known toward GAR Tfase. Contributing to its efficacious activity, compound 1 is effectively transported into the cell by the reduced folate carrier and intracellularly sequestered by polyglutamation. The crystal structure of human GAR Tfase with folate analogue 1 at 1.98 A resolution represents the first structure of any GAR Tfase to be determined with a cofactor or cofactor analogue without the presence of substrate. The folate-binding loop of residues 141-146, which is highly flexible in both Escherichia coli and unliganded human GAR Tfase structures, becomes highly ordered upon binding 1 in the folate-binding site. Computational docking of the natural cofactor into this and other apo or complexed structures provides a rational basis for modeling how the natural cofactor 10-formyltetrahydrofolic acid interacts with GAR Tfase, and suggests that this folate analogue-bound conformation represents the best template to date for inhibitor design.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12742019,

title = {Structural basis for antibody catalysis of a cationic cyclization reaction},

author = {Xueyong Zhu and Andreas Heine and Frédéric Monnat and K N Houk and Kim D Janda and Ian A Wilson},

doi = {10.1016/s0022-2836(03)00406-6},

issn = {0022-2836},

year  = {2003},

date = {2003-05-01},

journal = {J Mol Biol},

volume = {329},

number = {1},

pages = {69--83},

abstract = {Antibody 4C6 efficiently catalyzes a cationic cyclization reaction. Crystal structures of the antibody 4C6 Fab in complex with benzoic acid and in complex with its eliciting hapten were determined to 1.30A and 2.45A resolution, respectively. These crystal structures, together with computational analysis, have elucidated a possible mechanism for the monocyclization reaction. The hapten complex revealed a combining site pocket with high shape complementarity to the hapten. This active site cleft is dominated by aromatic residues that shield the highly reactive carbocation intermediates from solvent and stabilize the carbocation intermediates through cation-pi interactions. Modeling of an acyclic olefinic sulfonate ester substrate and the transition state (TS) structures shows that the chair-like transition state is favored, and trapping by water directly produces trans-2-(dimethylphenylsilyl)-cyclohexanol, whereas the less favored boat-like transition state leads to cyclohexene. The only significant change observed upon hapten binding is a side-chain rotation of Trp(L89), which reorients to form the base of the combining site. Intriguingly, a benzoic acid molecule was sequestered in the combining site of the unliganded antibody. The 4C6 active site was compared to that observed in a previously reported tandem cyclization antibody 19A4 hapten complex. These cationic cyclization antibodies exhibit convergent structural features with terpenoid cyclases that appear to be important for catalysis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12719582,

title = {Hyperglycosylated mutants of human immunodeficiency virus (HIV) type 1 monomeric gp120 as novel antigens for HIV vaccine design},

author = {Ralph Pantophlet and Ian A Wilson and Dennis R Burton},

doi = {10.1128/jvi.77.10.5889-5901.2003},

issn = {0022-538X},

year  = {2003},

date = {2003-05-01},

journal = {J Virol},

volume = {77},

number = {10},

pages = {5889--5901},

abstract = {The ability to induce broadly neutralizing antibodies should be a key component of any forthcoming vaccine against human immunodeficiency virus type 1. One potential vaccine candidate, monomeric gp120, has generally failed to elicit such antibodies. We postulated that gp120 might be a better immunogen if it could be engineered to preferentially bind known broadly neutralizing antibodies. In a first study, we found that four alanine substitutions on the perimeter of the so-called Phe-43 cavity of gp120 could reduce binding of weakly neutralizing CD4-binding site antibodies (R. Pantophlet, E. O. Saphire, P. Poignard, P. W. H. I. Parren, I. A. Wilson, and D. R. Burton, J. Virol. 77:642-658, 2003), while slightly enhancing binding of the potent, broadly neutralizing antibody b12. In the present study, we sought to reduce or abolish the binding of a wider range of nonneutralizing antibodies, by incorporating extra N-glycosylation motifs at select positions into the hypervariable loops and the gp120 core. A hyperglycosylated mutant containing seven extra glycosylation sequons (consensus sequences) and the four alanine substitutions described above did not bind an extensive panel of nonneutralizing and weakly neutralizing antibodies, including a polyclonal immunoglobulin preparation (HIVIG) of low neutralizing potency. Binding of b12, at lowered affinity, and of four antibodies to the C1 and C5 regions was maintained. Removal of N- and C-terminal residues in the C1 and C5 regions, respectively, reduced or abolished binding of the four antibodies, but this also adversely affected b12 binding. The hyperglycosylated mutant and its analogues described here are novel antigens that may provide a new approach to eliciting antibodies with b12-like neutralizing properties.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12670660,

title = {Directed evolution of N-acetylneuraminic acid aldolase to catalyze enantiomeric aldol reactions},

author = {Masaru Wada and Che-Chang Hsu and Dirk Franke and Michael Mitchell and Andreas Heine and Ian Wilson and Chi-Huey Wong},

doi = {10.1016/s0968-0896(03)00052-x},

issn = {0968-0896},

year  = {2003},

date = {2003-05-01},

journal = {Bioorg Med Chem},

volume = {11},

number = {9},

pages = {2091--2098},

abstract = {Expanding the scope of substrate specificity and stereoselectivity is of current interest in enzyme catalysis. Using error-prone PCR for in vitro directed evolution, the Neu5Ac aldolase from Escherichia coli has been altered to improve its catalytic activity toward enantiomeric substrates including N-acetyl-L-mannosamine and L-arabinose to produce L-sialic acid and L-KDO, the mirror-image sugars of the corresponding naturally occurring D-sugars. The first generation variant containing two mutations (Tyr98His and Phe115Leu) outside the (alpha,beta)(8)-barrel active site exhibits an inversion of enantioselectivity toward KDO and the second generation variant contains an additional amino acid change Val251Ile outside the alpha,beta-barrel active site that improves the enantiomeric formation of L-sialic acid and L-KDO. The X-ray structure of the triple mutant epNanA.2.5 at 2.3A resolution showed no significant difference between the wild-type and the mutant enzymes. We probed the potential structural 'hot spot' of enantioselectivity with saturation mutagenesis at Val251, the mutated residue most proximal to the Schiff base forming Lys165. The selected variant had an increase in k(cat) via replacement with another hydrophobic residue, leucine. Further sampling of a larger sequence space with error-prone PCR selected a third generation variant with significant improvement in L-KDO catalysis and a complete reversal of enantioselectivity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12719580,

title = {Molecular features of the broadly neutralizing immunoglobulin G1 b12 required for recognition of human immunodeficiency virus type 1 gp120},

author = {Michael B Zwick and Paul W H I Parren and Erica O Saphire and Sarah Church and Meng Wang and Jamie K Scott and Philip E Dawson and Ian A Wilson and Dennis R Burton},

doi = {10.1128/jvi.77.10.5863-5876.2003},

issn = {0022-538X},

year  = {2003},

date = {2003-05-01},

journal = {J Virol},

volume = {77},

number = {10},

pages = {5863--5876},

abstract = {IgG1 b12 is a broadly neutralizing antibody against human immunodeficiency virus type 1 (HIV-1). The epitope recognized by b12 overlaps the CD4 receptor-binding site (CD4bs) on gp120 and has been a target for vaccine design. Determination of the three-dimensional structure of immunoglobulin G1 (IgG1) b12 allowed modeling of the b12-gp120 interaction in which the protruding third complementarity-determining region (CDR) of the heavy chain (H3) was crucial for antibody binding. In the present study, extensive mutational analysis of the antigen-binding site of Fab b12 was carried out to investigate the validity of the model and to identify residues important for gp120 recognition and, by inference, key to the anti-HIV-1 activity of IgG1 b12. In all, 50 mutations were tested: 40 in H3, 4 each in H2 and L1, and 2 in L3. The results suggest that the interaction of gp120 with H3 of b12 is crucially dependent not only on a Trp residue at the apex of the H3 loop but also on a number of residues at the base of the loop. The arrangement of these residues, including aromatic side chains and side chains that hydrogen bond across the base of the loop, may rigidify H3 for penetration of the recessed CD4-binding cavity. The results further emphasize the importance to gp120 binding of a Tyr residue at the apex of the H2 loop that forms a second finger-like structure and a number of Arg residues in L1 that form a positively charged, shelf-like structure. In general, the data are consistent with the b12-gp120 interaction model previously proposed. At the gene level, somatic mutation is seen to be crucial for the generation of many of the structural features described. The Fab b12 mutants were also tested against the b12 epitope-mimic peptide B2.1, and the reactivity profile had many similarities but also significant differences from that observed for gp120. The paratope map of b12 may facilitate the design of molecules that are able to elicit b12-like activities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12672694,

title = {XOL-1, primary determinant of sexual fate in C. elegans, is a GHMP kinase family member and a structural prototype for a class of developmental regulators},

author = {John Gately Luz and Christian A Hassig and Catherine Pickle and Adam Godzik and Barbara J Meyer and Ian A Wilson},

doi = {10.1101/gad.1082303},

issn = {0890-9369},

year  = {2003},

date = {2003-04-01},

journal = {Genes Dev},

volume = {17},

number = {8},

pages = {977--990},

abstract = {In Caenorhabditis elegans, an X chromosome-counting mechanism specifies sexual fate. Specific genes termed X-signal elements, which are present on the X chromosome, act in a concerted dose-dependent fashion to regulate levels of the developmental switch gene xol-1. In turn, xol-1 levels determine sexual fate and the activation state of the dosage compensation mechanism. The crystal structure of the XOL-1 protein at 1.55 A resolution unexpectedly reveals that xol-1 encodes a GHMP kinase family member, despite sequence identity of 10% or less. Because GHMP kinases, thus far, have only been characterized as small molecule kinases involved in metabolic pathways, for example, amino acid and cholesterol synthesis, XOL-1 is the first member that controls nonmetabolic processes. Biochemical investigations demonstrated that XOL-1 does not bind ATP under standard conditions, suggesting that XOL-1 acts by a mechanism distinct from that of other GHMP kinases. In addition, we have cloned a XOL-1 ortholog from Caenorhabditis briggsae, a related nematode that diverged from C. elegans approximately 50-100 million years ago. These findings demonstrate an unanticipated role for GHMP kinase family members as mediators of sexual differentiation and dosage compensation and, possibly, other aspects of differentiation and development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12623022,

title = {Geranylgeranyl switching regulates GDI-Rab GTPase recycling},

author = {Yu An and Ying Shao and Christelle Alory and Jeanne Matteson and Toshiaki Sakisaka and Wei Chen and Richard A Gibbs and Ian A Wilson and William E Balch},

doi = {10.1016/s0969-2126(03)00034-0},

issn = {0969-2126},

year  = {2003},

date = {2003-03-01},

journal = {Structure},

volume = {11},

number = {3},

pages = {347--357},

abstract = {Rab GTPases, key regulators of membrane targeting and fusion, require the covalent attachment of geranylgeranyl lipids to their C terminus for function. To elucidate the role of lipid in Rab recycling, we have determined the crystal structure of Rab guanine nucleotide dissociation inhibitor (alphaGDI) in complex with a geranylgeranyl (GG) ligand (H(2)N-Cys-(S-GG)-OMe). The lipid is bound beneath the Rab binding platform in a shallow hydrophobic groove. Mutation of the binding pocket in the brain-specific alphaGDI leads to mental retardation. Strikingly, lipid binding acts through a conserved allosteric switching mechanism to promote release of the GDI-Rab[GDP] complex from the membrane.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12589760,

title = {Crystal structure of MHC class II I-Ab in complex with a human CLIP peptide: prediction of an I-Ab peptide-binding motif},

author = {Yuerong Zhu and Alexander Y Rudensky and Adam L Corper and Luc Teyton and Ian A Wilson},

doi = {10.1016/s0022-2836(02)01437-7},

issn = {0022-2836},

year  = {2003},

date = {2003-02-01},

journal = {J Mol Biol},

volume = {326},

number = {4},

pages = {1157--1174},

abstract = {Association between the class II major histocompatibility complex (MHC) and the class II invariant chain-associated peptide (CLIP) occurs naturally as an intermediate step in the MHC class II processing pathway. Here, we report the crystal structure of the murine class II MHC molecule I-A(b) in complex with human CLIP at 2.15A resolution. The structure of I-A(b) accounts, via the peptide-binding groove's unique physicochemistry, for the distinct peptide repertoire bound by this allele. CLIP adopts a similar conformation to peptides bound by other I-A alleles, reinforcing the notion that CLIP is presented as a conventional peptide antigen. When compared to the related HLA-DR3/CLIP complex structure, the CLIP peptide displays a slightly different conformation and distinct interaction pattern with residues in I-A(b). In addition, after examining the published sequences of peptides presented by I-A(b), we discuss the possibility of predicting peptide alignment in the I-A(b) binding groove using a simple scoring matrix.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}