1rhh
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The human monoclonal antibody Fab X5 neutralizes a broad range of HIV-1 | + | The human monoclonal antibody Fab X5 neutralizes a broad range of HIV-1 primary isolates. The crystal structure of X5 has been determined at 1.9 A resolution. There are two crystallographically independent Fab fragments in the asymmetric unit. The crystallographic R value for the final model is 0.22. The antibody-combining site features a long (22 amino acid residues) CDR H3 with a protruding hook-shaped motif. The X5 structure and site-directed mutagenesis data suggest that X5 amino acid residues W100 and Y100F in the CDR H3 motif may be critical for the binding of Fab X5 to gp120. X5 bound to a complex of a CD4 mimetic and gp120 with approximately the same kinetics and affinity as to a CD4-gp120 complex, suggesting that specific interactions between CD4 and X5 are unlikely to contribute to the binding of X5 to gp120-CD4 complexes. Binding of X5 to alanine scanning mutants of gp120JR-CSF complexed with CD4 suggested a critical role of the highly conserved amino acid residues at positions 423 and 432. The X5 structure and fine mapping of its epitope may assist in the elucidation of the mechanisms of viral entry and neutralization, and the development of HIV-1 inhibitors and vaccines. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Andrykovitch, M.]] | [[Category: Andrykovitch, M.]] | ||
| - | [[Category: Burton, D | + | [[Category: Burton, D R.]] |
[[Category: Darbha, R.]] | [[Category: Darbha, R.]] | ||
| - | [[Category: Dimitrov, D | + | [[Category: Dimitrov, D S.]] |
[[Category: Gu, Y.]] | [[Category: Gu, Y.]] | ||
[[Category: Ji, X.]] | [[Category: Ji, X.]] | ||
| - | [[Category: Labrijn, A | + | [[Category: Labrijn, A F.]] |
[[Category: Martin, L.]] | [[Category: Martin, L.]] | ||
[[Category: Pantophlet, R.]] | [[Category: Pantophlet, R.]] | ||
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[[Category: Shu, Y.]] | [[Category: Shu, Y.]] | ||
[[Category: Vita, C.]] | [[Category: Vita, C.]] | ||
| - | [[Category: Zhang, M | + | [[Category: Zhang, M Y.]] |
[[Category: antibody]] | [[Category: antibody]] | ||
[[Category: broadly neutralizing]] | [[Category: broadly neutralizing]] | ||
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[[Category: x5]] | [[Category: x5]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:50:56 2008'' |
Revision as of 12:50, 21 February 2008
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Crystal Structure of the Broadly HIV-1 Neutralizing Fab X5 at 1.90 Angstrom Resolution
Overview
The human monoclonal antibody Fab X5 neutralizes a broad range of HIV-1 primary isolates. The crystal structure of X5 has been determined at 1.9 A resolution. There are two crystallographically independent Fab fragments in the asymmetric unit. The crystallographic R value for the final model is 0.22. The antibody-combining site features a long (22 amino acid residues) CDR H3 with a protruding hook-shaped motif. The X5 structure and site-directed mutagenesis data suggest that X5 amino acid residues W100 and Y100F in the CDR H3 motif may be critical for the binding of Fab X5 to gp120. X5 bound to a complex of a CD4 mimetic and gp120 with approximately the same kinetics and affinity as to a CD4-gp120 complex, suggesting that specific interactions between CD4 and X5 are unlikely to contribute to the binding of X5 to gp120-CD4 complexes. Binding of X5 to alanine scanning mutants of gp120JR-CSF complexed with CD4 suggested a critical role of the highly conserved amino acid residues at positions 423 and 432. The X5 structure and fine mapping of its epitope may assist in the elucidation of the mechanisms of viral entry and neutralization, and the development of HIV-1 inhibitors and vaccines.
About this Structure
1RHH is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the broadly cross-reactive HIV-1-neutralizing Fab X5 and fine mapping of its epitope., Darbha R, Phogat S, Labrijn AF, Shu Y, Gu Y, Andrykovitch M, Zhang MY, Pantophlet R, Martin L, Vita C, Burton DR, Dimitrov DS, Ji X, Biochemistry. 2004 Feb 17;43(6):1410-7. PMID:14769016
Page seeded by OCA on Thu Feb 21 14:50:56 2008
Categories: Homo sapiens | Protein complex | Andrykovitch, M. | Burton, D R. | Darbha, R. | Dimitrov, D S. | Gu, Y. | Ji, X. | Labrijn, A F. | Martin, L. | Pantophlet, R. | Phogat, S. | Shu, Y. | Vita, C. | Zhang, M Y. | Antibody | Broadly neutralizing | Fab | Hiv-1 | X5
