6otg

HIV-1 protease triple mutants V32I, I47V, V82I with GRL-011-11A (a methylamine bis-Tetrahydrofuran P2-Ligand, sulfonamide isostere derivate)

spinqualitylabelsall models 6otg, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6otg is a 2 chain structure with sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.5Å Ligands: 4UY, FMT, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q7SSI0_9HIV1 Publication Abstract from PubMed HIV-1 protease inhibitors are effective in HIV/AIDS therapy, although drug resistance is a severe problem. This study examines the effects of four investigational inhibitors against HIV-1 protease with drug resistant mutations of V32I, I47V and V82I (PRTri) that model the inhibitor-binding site of HIV-2 protease. These inhibitors contain diverse chemical modifications on the darunavir scaffold and form new interactions with wild type protease, however, the measured inhibition constants for PRTri mutant range from 17 to 40nM or significantly worse than picomolar values reported for wild type enzyme. The X-ray crystal structure of PRTri mutant in complex with inhibitor 1at 1.5A resolution shows minor changes in interactions with inhibitor compared with the corresponding wild type PR complex. Instead, the basic amine at P2 of inhibitor together with mutation V82I induces two alternate conformations for the side chain of Arg8 with new interactions with inhibitor and Leu10. Hence, inhibition is influenced by small coordinated changes in hydrophobic interactions. Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I.,Pawar S, Wang YF, Wong-Sam A, Agniswamy J, Ghosh AK, Harrison RW, Weber IT Biochem Biophys Res Commun. 2019 May 12. pii: S0006-291X(19)30934-9. doi:, 10.1016/j.bbrc.2019.05.064. PMID:31092330 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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