1czq: Difference between revisions

Revision as of 13:17, 2 May 2008

CRYSTAL STRUCTURE OF THE D10-P1/IQN17 COMPLEX: A D-PEPTIDE INHIBITOR OF HIV-1 ENTRY BOUND TO THE GP41 COILED-COIL POCKET.

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

1CZQ is a Single protein structure of sequence from Saccharomyces cerevisiae and human immunodeficiency virus. 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 Page seeded by OCA on Fri May 2 13:17:01 2008

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OCA

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 [[Image:1czq.gif|left|200px]]
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 '''CRYSTAL STRUCTURE OF THE D10-P1/IQN17 COMPLEX: A D-PEPTIDE INHIBITOR OF HIV-1 ENTRY BOUND TO THE GP41 COILED-COIL POCKET.'''
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 [[Category: Kim, P S.]]
 [[Category: Malashkevich, V N.]]
-[[Category: coiled coil]]
+[[Category: Coiled coil]]
-[[Category: envelope glycoprotein]]
+[[Category: Envelope glycoprotein]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 13:17:01 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:31:37 2008''