2R3C

Structure of the gp41 N-peptide in complex with the HIV entry inhibitor PIE1

Summary for 2R3C

• Entry DOI: 10.2210/pdb2r3c/pdb
• Related: 2R5B 2R5D
• Related PRD ID: PRD_000280
• Descriptor: gp41 N-peptide, HIV entry inhibitor PIE1, YTTRIUM (III) ION, ... (5 entities in total)
• Functional Keywords: hiv, inhibitor, viral entry, pie, viral protein, viral protein-viral protein inhibitor complex, viral protein/viral protein inhibitor
• Biological source: synthetic construct; More
• Total number of polymer chains: 4
• Total formula weight: 15075.34

Authors

VanDemark, A.P.,Welch, B.,Heroux, A.,Hill, C.P.,Kay, M.S. (deposition date: 2007-08-29, release date: 2007-10-02, Last modification date: 2018-08-08)

Primary citation

Welch, B.D.,Vandemark, A.P.,Heroux, A.,Hill, C.P.,Kay, M.S.
Potent D-peptide inhibitors of HIV-1 entry
Proc.Natl.Acad.Sci.Usa, 104:16828-16833, 2007

PubMed Abstract: 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.

PubMed: 17942675
DOI: 10.1073/pnas.0708109104

Experimental method

X-RAY DIFFRACTION (1.73 Å)