Crystal structure of the HIV-1 integrase core domain in complex with sucrose reveals details of an allosteric inhibitory binding site

HIV integrase (IN) is an essential enzyme in HIV replication and an important target for drug design. IN has been shown to interact with a number of cellular and viral proteins during the integration process. Disruption of these important interactions could provide a mechanism for allosteric inhibit...

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Veröffentlicht in:	FEBS letters 2010-04, Vol.584 (8), p.1455-1462
Hauptverfasser:	Wielens, Jerome, Headey, Stephen J., Jeevarajah, Dharshini, Rhodes, David I., Deadman, John, Chalmers, David K., Scanlon, Martin J., Parker, Michael W.
Format:	Artikel
Sprache:	eng
Schlagworte:	AIDS VIRUS Allosteric Regulation Anti-HIV drug Binding Sites CRYSTAL STRUCTURE Crystallography, X-Ray DESIGN DIMERS Drug Discovery ENZYMES Glycerol - metabolism HIV Integrase - chemistry HIV Integrase - genetics HIV Integrase - isolation & purification HIV Integrase - metabolism HIV Integrase Inhibitors - chemistry HIV Integrase Inhibitors - metabolism HIV Integrase Inhibitors - pharmacology HIV-1 - drug effects HIV-1 - enzymology HIV-1 - physiology HIV-1 integrase Human immunodeficiency virus 1 Ligand binding MATERIALS SCIENCE Models, Molecular Protein Binding Protein Multimerization Protein Structure, Quaternary Protein Structure, Tertiary PROTEINS RESOLUTION SACCHAROSE Sucrose - metabolism TARGETS Virus Replication - drug effects X-ray crystallography
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Zusammenfassung:	HIV integrase (IN) is an essential enzyme in HIV replication and an important target for drug design. IN has been shown to interact with a number of cellular and viral proteins during the integration process. Disruption of these important interactions could provide a mechanism for allosteric inhibition of IN. We present the highest resolution crystal structure of the IN core domain to date. We also present a crystal structure of the IN core domain in complex with sucrose which is bound at the dimer interface in a region that has previously been reported to bind integrase inhibitors. MINT- 7713125: IN (uniprotkb: P04585) and IN (uniprotkb: P04585) bind (MI: 0407) by X-ray crystallography (MI: 0114)
ISSN:	0014-5793 1873-3468
DOI:	10.1016/j.febslet.2010.03.016