2r5d: Difference between revisions
New page: left|200px<br /><applet load="2r5d" size="350" color="white" frame="true" align="right" spinBox="true" caption="2r5d, resolution 1.660Å" /> '''Structure of the gp... |
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==Overview== | ==Overview== | ||
During HIV-1 entry, the highly conserved gp41 N-trimer pocket region | During HIV-1 entry, the highly conserved gp41 N-trimer pocket region becomes transiently exposed and vulnerable to inhibition. Using mirror-image phage display and structure-assisted design, we have discovered protease-resistant D-amino acid peptides (D-peptides) that bind the N-trimer pocket with high affinity and potently inhibit viral entry. We also report high-resolution crystal structures of two of these D-peptides in complex with a pocket mimic that suggest sources of their high potency. A trimeric version of one of these peptides is the most potent pocket-specific entry inhibitor yet reported by three orders of magnitude (IC(50) = 250 pM). These results are the first demonstration that D-peptides can form specific and high-affinity interactions with natural protein targets and strengthen their promise as therapeutic agents. The D-peptides described here address limitations associated with current L-peptide entry inhibitors and are promising leads for the prevention and treatment of HIV/AIDS. | ||
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
Potent D-peptide inhibitors of HIV-1 entry., Welch BD, | Potent D-peptide inhibitors of HIV-1 entry., Welch BD, VanDemark AP, Heroux A, Hill CP, Kay MS, Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16828-33. Epub 2007 Oct 17. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17942675 17942675] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Heroux, A.]] | [[Category: Heroux, A.]] | ||
[[Category: Hill, C | [[Category: Hill, C P.]] | ||
[[Category: Kay, M | [[Category: Kay, M S.]] | ||
[[Category: VanDemark, A | [[Category: VanDemark, A P.]] | ||
[[Category: Welch, B.]] | [[Category: Welch, B.]] | ||
[[Category: ACE]] | [[Category: ACE]] | ||
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[[Category: viral protein]] | [[Category: viral protein]] | ||
''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 18:44:45 2008'' | ||
Revision as of 19:44, 21 February 2008
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Structure of the gp41 N-trimer in complex with the HIV entry inhibitor PIE7
OverviewOverview
During HIV-1 entry, the highly conserved gp41 N-trimer pocket region becomes transiently exposed and vulnerable to inhibition. Using mirror-image phage display and structure-assisted design, we have discovered protease-resistant D-amino acid peptides (D-peptides) that bind the N-trimer pocket with high affinity and potently inhibit viral entry. We also report high-resolution crystal structures of two of these D-peptides in complex with a pocket mimic that suggest sources of their high potency. A trimeric version of one of these peptides is the most potent pocket-specific entry inhibitor yet reported by three orders of magnitude (IC(50) = 250 pM). These results are the first demonstration that D-peptides can form specific and high-affinity interactions with natural protein targets and strengthen their promise as therapeutic agents. The D-peptides described here address limitations associated with current L-peptide entry inhibitors and are promising leads for the prevention and treatment of HIV/AIDS.
About this StructureAbout this Structure
2R5D is a Protein complex structure of sequences from [1] with , , , and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Potent D-peptide inhibitors of HIV-1 entry., Welch BD, VanDemark AP, Heroux A, Hill CP, Kay MS, Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16828-33. Epub 2007 Oct 17. PMID:17942675
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