1czq
From Proteopedia
(New page: 200px<br /> <applet load="1czq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1czq, resolution 1.50Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1czq.gif|left|200px]]<br /> | + | [[Image:1czq.gif|left|200px]]<br /><applet load="1czq" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1czq" size=" | + | |
caption="1czq, resolution 1.50Å" /> | caption="1czq, resolution 1.50Å" /> | ||
'''CRYSTAL STRUCTURE OF THE D10-P1/IQN17 COMPLEX: A D-PEPTIDE INHIBITOR OF HIV-1 ENTRY BOUND TO THE GP41 COILED-COIL POCKET.'''<br /> | '''CRYSTAL STRUCTURE OF THE D10-P1/IQN17 COMPLEX: A D-PEPTIDE INHIBITOR OF HIV-1 ENTRY BOUND TO THE GP41 COILED-COIL POCKET.'''<br /> | ||
==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== | ||
| - | 1CZQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_and_human_immunodeficiency_virus Saccharomyces cerevisiae and human immunodeficiency virus] with CL and ACE as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1CZQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_and_human_immunodeficiency_virus Saccharomyces cerevisiae and human immunodeficiency virus] with <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=ACE:'>ACE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CZQ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Saccharomyces cerevisiae and human immunodeficiency virus]] | [[Category: Saccharomyces cerevisiae and human immunodeficiency virus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Carr, P | + | [[Category: Carr, P A.]] |
| - | [[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: envelope glycoprotein]] | [[Category: envelope glycoprotein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:11:21 2008'' |
Revision as of 10:11, 21 February 2008
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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.
Overview
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
1CZQ is a Single protein structure of sequence from Saccharomyces cerevisiae and human immunodeficiency virus with and as ligands. Full crystallographic information is available from OCA.
Reference
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 Thu Feb 21 12:11:21 2008
