2r5d | pdb_00002r5d
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| 2r5d, resolution 1.660Å | |||||||||||||
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| Ligands: | ACE, DAL, DAS, DCY, DGL, DGN, DLE, DLY, DPR, DTR, DTY, EPE, GOL, NH2, SO4 | ||||||||||||
| Related: | 2R3C, 2R5B
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
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
2R5D is a Protein complex structure of sequences from [1]. 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 Mon Mar 31 04:56:43 2008
