1l7i
From Proteopedia
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|PDB= 1l7i |SIZE=350|CAPTION= <scene name='initialview01'>1l7i</scene>, resolution 1.80Å | |PDB= 1l7i |SIZE=350|CAPTION= <scene name='initialview01'>1l7i</scene>, resolution 1.80Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene> | + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1l7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l7i OCA], [http://www.ebi.ac.uk/pdbsum/1l7i PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1l7i RCSB]</span> | ||
}} | }} | ||
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[[Category: Vajdos, F F.]] | [[Category: Vajdos, F F.]] | ||
[[Category: Vos, A M.de.]] | [[Category: Vos, A M.de.]] | ||
| - | [[Category: SO4]] | ||
[[Category: fab fragment]] | [[Category: fab fragment]] | ||
[[Category: ig domain]] | [[Category: ig domain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:59:13 2008'' |
Revision as of 18:59, 30 March 2008
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| , resolution 1.80Å | |||||||
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| Ligands: | |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of the anti-ErbB2 Fab2C4
Overview
Shotgun scanning combinatorial mutagenesis was used to study the antigen-binding site of Fab2C4, a humanized monoclonal antibody fragment that binds to the extracellular domain of the human oncogene product ErbB2. Essentially all the residues in the Fab2C4 complementarity determining regions (CDRs) were alanine-scanned using phage-displayed libraries that preferentially allowed side-chains to vary as the wild-type or alanine. A separate homolog-scan was performed using libraries that allowed side-chains to vary only as the wild-type or a similar amino acid residue. Following binding selections to isolate functional clones, DNA sequencing was used to determine the wild-type/mutant ratios at each varied position, and these ratios were used to assess the contributions of each side-chain to antigen binding. The alanine-scan revealed that most of the side-chains that contribute to antigen binding are located in the heavy chain, and the Fab2C4 three-dimensional structure revealed that these residues fall into two groups. The first group consists of solvent-exposed residues which likely make energetically favorable contacts with the antigen and thus comprise the functional-binding epitope. The second group consists of buried residues with side-chains that pack against other CDR residues and apparently act as scaffolding to maintain the functional epitope in a binding-competent conformation. The homolog-scan involved subtle mutations, and as a result, only a subset of the side-chains that were intolerant to alanine substitutions were also intolerant to homologous substitutions. In particular, the 610 A2 functional epitope surface revealed by alanine-scanning shrunk to only 369 A2 when mapped with homologous substitutions, suggesting that this smaller subset of side-chains may be involved in more precise contacts with the antigen. The results validate shotgun scanning as a rapid and accurate method for determining the functional contributions of individual side-chains involved in protein-protein interactions.
About this Structure
1L7I is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Comprehensive functional maps of the antigen-binding site of an anti-ErbB2 antibody obtained with shotgun scanning mutagenesis., Vajdos FF, Adams CW, Breece TN, Presta LG, de Vos AM, Sidhu SS, J Mol Biol. 2002 Jul 5;320(2):415-28. PMID:12079396
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