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2r5b
From Proteopedia
(New page: 200px<br /><applet load="2r5b" size="350" color="white" frame="true" align="right" spinBox="true" caption="2r5b, resolution 2.000Å" /> '''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 18:44:46 2008'' |
Revision as of 16:44, 21 February 2008
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Structure of the gp41 N-trimer in complex with the HIV entry inhibitor PIE7
Overview
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
2R5B is a Protein complex structure of sequences from [1] with , and as ligands. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 18:44:46 2008
Categories: Protein complex | Heroux, A. | Hill, C P. | Kay, M S. | VanDemark, A P. | Welch, B. | ACE | NH2 | SO4 | Hiv | Inhibitor | Peptide | Pie | Viral entry | Viral protein
