2b4j

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{{STRUCTURE_2b4j| PDB=2b4j | SCENE= }}
{{STRUCTURE_2b4j| PDB=2b4j | SCENE= }}
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'''Structural basis for the recognition between HIV-1 integrase and LEDGF/p75'''
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===Structural basis for the recognition between HIV-1 integrase and LEDGF/p75===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_16260736}}
==About this Structure==
==About this Structure==
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:50:45 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:40:02 2008''

Revision as of 00:40, 28 July 2008

Image:2b4j.png

Template:STRUCTURE 2b4j

Structural basis for the recognition between HIV-1 integrase and LEDGF/p75

Template:ABSTRACT PUBMED 16260736

About this Structure

2B4J is a Protein complex structure of sequences from Homo sapiens and Human immunodeficiency virus 1. 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

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