4be2

PFV intasome with inhibitor XZ-259

spinqualitylabelsall models 4be2, resolution 2.38Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4be2 is a 4 chain structure with sequence from Human spumaretrovirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, MG, SO4, XZ2, ZN Related: 2x6n, 2x6s, 2x74, 2x78, 4bac, 4bdy, 4bdz, 4be0, 4be1 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Based on a series of lactam and phthalimide derivatives that inhibit HIV-1 integrase, we developed a new derivative, XZ-259, with biochemical and antiviral activities comparable to raltegravir. We determined the crystal structures of XZ-259 and four other derivatives in complex with the prototype foamy virus intasome. The compounds bind at the integrase-Mg2+-DNA interface of the integrase active site. In biochemical and antiviral assays, XZ-259 inhibits raltegravir-resistant HIV-1 integrases harboring the Y143R mutation. Molecular modeling is also presented suggesting that XZ-259 can bind in the HIV-1 intasome with its dimethyl sulfonamide group adopting two opposite orientations. Molecular dynamics analyses of the HIV-1 intasome highlight the importance of the viral DNA in drug potency. Activities, crystal structures and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase.,Metifiot M, Maddali K, Johnson BC, Hare S, Smith SJ, Zhao XZ, Marchand C, Burke TR, Hughes SH, Cherepanov P, Pommier Y ACS Chem Biol. 2012 Oct 17. PMID:23075516 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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