2q5u: Difference between revisions
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==Overview== | ==Overview== | ||
The HIV-1 gp41 protein promotes viral entry by mediating the fusion of | The HIV-1 gp41 protein promotes viral entry by mediating the fusion of viral and cellular membranes. A prominent pocket on the surface of a central trimeric coiled coil within gp41 was previously identified as a potential target for drugs that inhibit HIV-1 entry. We designed a peptide, IQN17, which properly presents this pocket. Utilizing IQN17 and mirror-image phage display, we identified cyclic, D-peptide inhibitors of HIV-1 infection that share a sequence motif. A 1.5 A cocrystal structure of IQN17 in complex with a D-peptide, and NMR studies, show that conserved residues of these inhibitors make intimate contact with the gp41 pocket. Our studies validate the pocket per se as a target for drug development. IQN17 and these D-peptide inhibitors are likely to be useful for development and identification of a new class of orally bioavailable anti-HIV drugs. | ||
==About this Structure== | ==About this Structure== | ||
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Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket., Eckert DM, Malashkevich VN, Hong LH, Carr PA, Kim PS, Cell. 1999 Oct 1;99(1):103-15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10520998 10520998] | Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket., Eckert DM, Malashkevich VN, Hong LH, Carr PA, Kim PS, Cell. 1999 Oct 1;99(1):103-15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10520998 10520998] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Eckert, D | [[Category: Eckert, D M.]] | ||
[[Category: Hong, L | [[Category: Hong, L H.]] | ||
[[Category: Kim, P | [[Category: Kim, P S.]] | ||
[[Category: Malashkevich, V | [[Category: Malashkevich, V N.]] | ||
[[Category: ACE]] | [[Category: ACE]] | ||
[[Category: CL]] | [[Category: CL]] | ||
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[[Category: viral protein/viral protein inhibitor]] | [[Category: viral protein/viral protein inhibitor]] | ||
''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 18:36:21 2008'' | ||
Revision as of 19:36, 21 February 2008
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Crystal structure of IQN17
OverviewOverview
The HIV-1 gp41 protein promotes viral entry by mediating the fusion of viral and cellular membranes. A prominent pocket on the surface of a central trimeric coiled coil within gp41 was previously identified as a potential target for drugs that inhibit HIV-1 entry. We designed a peptide, IQN17, which properly presents this pocket. Utilizing IQN17 and mirror-image phage display, we identified cyclic, D-peptide inhibitors of HIV-1 infection that share a sequence motif. A 1.5 A cocrystal structure of IQN17 in complex with a D-peptide, and NMR studies, show that conserved residues of these inhibitors make intimate contact with the gp41 pocket. Our studies validate the pocket per se as a target for drug development. IQN17 and these D-peptide inhibitors are likely to be useful for development and identification of a new class of orally bioavailable anti-HIV drugs.
About this StructureAbout this Structure
2Q5U is a Single protein structure of sequence from [1] with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket., Eckert DM, Malashkevich VN, Hong LH, Carr PA, Kim PS, Cell. 1999 Oct 1;99(1):103-15. PMID:10520998
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