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Article: Crystal Structure of the Broadly Cross-Reactive HIV-1-Neutralizing Fab X5 and Fine Mapping of Its Epitope

TitleCrystal Structure of the Broadly Cross-Reactive HIV-1-Neutralizing Fab X5 and Fine Mapping of Its Epitope
Authors
Issue Date2004
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/biochemistry
Citation
Biochemistry, 2004, v. 43 n. 6, p. 1410-1417 How to Cite?
Abstract
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 Å 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.
Persistent Identifierhttp://hdl.handle.net/10722/157384
ISSN
2013 Impact Factor: 3.194
ISI Accession Number ID
References

 

Author Affiliations
  1. National Cancer Institute at Frederick
  2. Scripps Research Institute
  3. CEA Saclay
DC FieldValueLanguage
dc.contributor.authorDarbha, Ren_US
dc.contributor.authorPhogat, Sen_US
dc.contributor.authorLabrijn, AFen_US
dc.contributor.authorShu, Yen_US
dc.contributor.authorGu, Yen_US
dc.contributor.authorAndrykovitch, Men_US
dc.contributor.authorZhang, MYen_US
dc.contributor.authorPantophlet, Ren_US
dc.contributor.authorMartin, Len_US
dc.contributor.authorVita, Cen_US
dc.contributor.authorBurton, DRen_US
dc.contributor.authorDimitrov, DSen_US
dc.contributor.authorJi, Xen_US
dc.date.accessioned2012-08-08T08:49:31Z-
dc.date.available2012-08-08T08:49:31Z-
dc.date.issued2004en_US
dc.identifier.citationBiochemistry, 2004, v. 43 n. 6, p. 1410-1417en_US
dc.identifier.issn0006-2960en_US
dc.identifier.urihttp://hdl.handle.net/10722/157384-
dc.description.abstractThe 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 Å 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.en_US
dc.languageengen_US
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/biochemistryen_US
dc.relation.ispartofBiochemistryen_US
dc.subject.meshAntibodies, Monoclonal - Chemistry - Genetics - Metabolismen_US
dc.subject.meshAntigens, Cd4 - Chemistry - Immunology - Metabolismen_US
dc.subject.meshAntiviral Agents - Chemistry - Genetics - Metabolismen_US
dc.subject.meshBinding Sites - Geneticsen_US
dc.subject.meshCross Reactions - Geneticsen_US
dc.subject.meshCrystallizationen_US
dc.subject.meshCrystallography, X-Rayen_US
dc.subject.meshEpitopes - Chemistry - Immunology - Metabolismen_US
dc.subject.meshHiv Envelope Protein Gp120 - Chemistry - Genetics - Metabolismen_US
dc.subject.meshHiv-1 - Immunology - Pathogenicityen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoglobulin Fab Fragments - Chemistry - Genetics - Metabolismen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshMutagenesis, Site-Directeden_US
dc.subject.meshNeutralization Testsen_US
dc.subject.meshPeptide Mapping - Methodsen_US
dc.subject.meshProtein Structure, Tertiary - Geneticsen_US
dc.subject.meshSurface Plasmon Resonanceen_US
dc.titleCrystal Structure of the Broadly Cross-Reactive HIV-1-Neutralizing Fab X5 and Fine Mapping of Its Epitopeen_US
dc.typeArticleen_US
dc.identifier.emailZhang, MY:zhangmy@hku.hken_US
dc.identifier.authorityZhang, MY=rp01409en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1021/bi035323xen_US
dc.identifier.pmid14769016en_US
dc.identifier.scopuseid_2-s2.0-10744224411en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-10744224411&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume43en_US
dc.identifier.issue6en_US
dc.identifier.spage1410en_US
dc.identifier.epage1417en_US
dc.identifier.isiWOS:000188928500002-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridDarbha, R=6507597513en_US
dc.identifier.scopusauthoridPhogat, S=6602665528en_US
dc.identifier.scopusauthoridLabrijn, AF=6507797385en_US
dc.identifier.scopusauthoridShu, Y=7103239429en_US
dc.identifier.scopusauthoridGu, Y=7403046521en_US
dc.identifier.scopusauthoridAndrykovitch, M=6506851823en_US
dc.identifier.scopusauthoridZhang, MY=35316639300en_US
dc.identifier.scopusauthoridPantophlet, R=6602751605en_US
dc.identifier.scopusauthoridMartin, L=7403870482en_US
dc.identifier.scopusauthoridVita, C=7005957556en_US
dc.identifier.scopusauthoridBurton, DR=7401577043en_US
dc.identifier.scopusauthoridDimitrov, DS=7202564539en_US
dc.identifier.scopusauthoridJi, X=7402840134en_US

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