3lpt | pdb_00003lpt

HIV integrase

spinqualitylabelsall models 3lpt, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3lpt is a 1 chain structure with sequence from 9hiv1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 723, CA, CL, P03, PEG, SO4 NonStd Res: CAF Related: 1hyv, 3lpu Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Lens epithelium-derived growth factor (LEDGF/p75) is a cellular cofactor of HIV-1 integrase that promotes viral integration by tethering the preintegration complex to the chromatin. By virtue of its crucial role in the early steps of HIV replication, the interaction between LEDGF/p75 and integrase represents an attractive target for antiviral therapy. We have rationally designed a series of 2-(quinolin-3-yl)acetic acid derivatives (LEDGINs) that act as potent inhibitors of the LEDGF/p75-integrase interaction and HIV-1 replication at submicromolar concentration by blocking the integration step. A 1.84-A resolution crystal structure corroborates the binding of the inhibitor in the LEDGF/p75-binding pocket of integrase. Together with the lack of cross-resistance with two clinical integrase inhibitors, these findings define the 2-(quinolin-3-yl)acetic acid derivatives as the first genuine allosteric HIV-1 integrase inhibitors. Our work demonstrates the feasibility of rational design of small molecules inhibiting the protein-protein interaction between a viral protein and a cellular host factor. Rational design of small-molecule inhibitors of the LEDGF/p75-integrase interaction and HIV replication.,Christ F, Voet A, Marchand A, Nicolet S, Desimmie BA, Marchand D, Bardiot D, Van der Veken NJ, Van Remoortel B, Strelkov SV, De Maeyer M, Chaltin P, Debyser Z Nat Chem Biol. 2010 Jun;6(6):442-8. Epub 2010 May 16. PMID:20473303 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Retroviral integrase 3D structures

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