2oqj

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{{Seed}}
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{{STRUCTURE_2oqj| PDB=2oqj | SCENE= }}
{{STRUCTURE_2oqj| PDB=2oqj | SCENE= }}
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'''Crystal structure analysis of Fab 2G12 in complex with peptide 2G12.1'''
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===Crystal structure analysis of Fab 2G12 in complex with peptide 2G12.1===
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==Overview==
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MAb 2G12 neutralizes HIV-1 by binding with high affinity to a cluster of high-mannose oligosaccharides on the envelope glycoprotein, gp120. Screening of phage-displayed peptide libraries with 2G12 identified peptides that bind specifically, with K(d)s ranging from 0.4 to 200 microM. The crystal structure of a 21-mer peptide ligand in complex with 2G12 Fab was determined at 2.8 A resolution. Comparison of this structure with previous structures of 2G12-carbohydrate complexes revealed striking differences in the mechanism of 2G12 binding to peptide vs. carbohydrate. The peptide occupies a site different from, but adjacent to, the primary carbohydrate-binding site on 2G12, and makes only slightly fewer contacts to the Fab than Man(9)GlcNAc(2) (51 vs. 56, respectively). However, only two antibody contacts with the peptide are hydrogen bonds in contrast to six with Man(9)GlcNAc(2), and only three of the antibody residues that interact with Man(9)GlcNAc(2) also contact the peptide. Thus, this mechanism of peptide binding to 2G12 does not support structural mimicry of the native carbohydrate epitope on gp120, since it neither replicates the oligosaccharide footprint on the antibody nor most of the contact residues. Moreover, 2G12.1 peptide is not an immunogenic mimic of the 2G12 epitope, since antisera produced against it did not bind gp120.
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(as it appears on PubMed at http://www.pubmed.gov), where 18198210 is the PubMed ID number.
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{{ABSTRACT_PUBMED_18198210}}
==About this Structure==
==About this Structure==
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[[Category: Immune system]]
[[Category: Immune system]]
[[Category: Immunoglobulin fold]]
[[Category: Immunoglobulin fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 28 09:30:39 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:28:24 2008''

Revision as of 11:28, 29 July 2008

Image:2oqj.png

Template:STRUCTURE 2oqj

Crystal structure analysis of Fab 2G12 in complex with peptide 2G12.1

Template:ABSTRACT PUBMED 18198210

About this Structure

Full crystallographic information is available from OCA.

Reference

A peptide inhibitor of HIV-1 neutralizing antibody 2G12 is not a structural mimic of the natural carbohydrate epitope on gp120., Menendez A, Calarese DA, Stanfield RL, Chow KC, Scanlan CN, Kunert R, Katinger H, Burton DR, Wilson IA, Scott JK, FASEB J. 2008 May;22(5):1380-92. Epub 2008 Jan 15. PMID:18198210

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