2b4j
From Proteopedia
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Structural basis for the recognition between HIV-1 integrase and LEDGF/p75
Overview
Integrase (IN) is an essential retroviral enzyme, and human, transcriptional coactivator p75, which is also referred to as lens, epithelium-derived growth factor (LEDGF), is the dominant cellular binding, partner of HIV-1 IN. Here, we report the crystal structure of the dimeric, catalytic core domain of HIV-1 IN complexed to the IN-binding domain of, LEDGF. Previously identified LEDGF hotspot residues anchor the protein to, both monomers at the IN dimer interface. The principal structural features, of IN that are recognized by the host factor are the backbone conformation, of residues 168-171 from one monomer and a hydrophobic patch that is, primarily comprised of alpha-helices 1 and 3 of the second IN monomer., Inspection of diverse retroviral primary and secondary sequence elements, helps to explain the apparent lentiviral tropism of the LEDGF-IN, interaction. Because the lethal phenotypes of HIV-1 mutant viruses unable, to interact with LEDGF indicate that IN function is highly sensitive to, perturbations of the structure around the LEDGF-binding site, we propose, that small molecule inhibitors of the protein-protein interaction might, similarly disrupt HIV-1 replication.
About this Structure
2B4J is a Protein complex structure of sequences from Homo sapiens and Human immunodeficiency virus 1 with PO4 and GOL as ligands. Full crystallographic information is available from OCA.
Reference
Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75., Cherepanov P, Ambrosio AL, Rahman S, Ellenberger T, Engelman A, Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17308-13. Epub 2005 Oct 31. PMID:16260736
Page seeded by OCA on Thu Nov 8 14:42:53 2007
