3AVN

Crystal structures of novel allosteric peptide inhibitors of HIV integrase in the LEDGF binding site

Summary for 3AVN

• Entry DOI: 10.2210/pdb3avn/pdb
• Related: 3AV9 3AVA 3AVB 3AVC 3AVF 3AVG 3AVH 3AVI 3AVJ 3AVK 3AVL 3AVM
• Related PRD ID: PRD_000827
• Descriptor: Integrase, LEDGF peptide, SULFATE ION, ... (6 entities in total)
• Functional Keywords: protein-protein interactions, hiv, recombination-inhibitor complex, recombination/inhibitor
• Biological source: Human immunodeficiency virus type 1 (HIV-1); More
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P12497
• Total number of polymer chains: 4
• Total formula weight: 42934.89

Authors

Peat, T.S.,Deadman, J.J.,Newman, J.,Rhodes, D.I. (deposition date: 2011-03-05, release date: 2012-01-18, Last modification date: 2024-10-30)

Primary citation

Rhodes, D.I.,Peat, T.S.,Vandegraaff, N.,Jeevarajah, D.,Newman, J.,Martyn, J.,Coates, J.A.,Ede, N.J.,Rea, P.,Deadman, J.J.
Crystal structures of novel allosteric peptide inhibitors of HIV integrase identify new interactions at the LEDGF binding site.
Chembiochem, 12:2311-2315, 2011

PubMed Abstract: An optimised method of solution cyclisation gave us access to a series of peptides including SLKIDNLD (2). We investigated the crystallographic complexes of the HIV integrase (HIV-IN) catalytic core domain with 13 of the peptides and identified multiple interactions at the binding site, including hydrogen bonds with residues Thr125 and Gln95, that have not previously been described as being accessible within the binding site. We show that the peptides inhibit the interaction of lens epithelium-derived growth factor (LEDGF) with HIV-IN in a proximity AlphaScreen assay and in an assay for the LEDGF enhancement of HIV-IN strand transfer. The interactions identified represent a potential framework for the development of new HIV-IN inhibitors.

PubMed: 21850718
DOI: 10.1002/cbic.201100350

Experimental method

X-RAY DIFFRACTION (2.1 Å)