2qd7 | pdb_00002qd7

HIV-1 Protease Mutant V82A with potent Antiviral inhibitor GRL-98065

spinqualitylabelsall models 2qd7, resolution 1.11Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2qd7 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. Ligands: 065, DMS, GOL, PO4 Related: 2z4o, 2qci, 2qd6, 2qd8 Activity: HIV-1 retropepsin, with EC number 3.4.23.16 Resources: FirstGlance, OCA, RCSB, PDBsum 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 The potent new antiviral inhibitor GRL-98065 (1) of HIV-1 protease (PR) has been studied with PR variants containing the single mutations D30N, I50V, V82A, and I84V that provide resistance to the major clinical inhibitors. Compound 1 had inhibition constants of 17-fold, 8-fold, 3-fold, and 3-fold, respectively, for PR(D30N), PR(I50V), PR(V82A), and PR(I84V) relative to wild type PR. The chemically related darunavir had similar relative inhibition, except for PR(D30N), where inhibitor 1 was approximately 3-fold less potent. The high resolution (1.11-1.60 Angstrom) crystal structures of PR mutant complexes with inhibitor 1 showed small changes relative to the wild type enzyme. PR(D30N) and PR(V82A) showed compensating interactions with inhibitor 1 relative to those of PR, while reduced hydrophobic contacts were observed with PR(I50V) and PR(I84V). Importantly, inhibitor 1 complexes showed fewer changes relative to wild type enzyme than reported for darunavir complexes. Therefore, inhibitor 1 is a valuable addition to the antiviral inhibitors with high potency against resistant strains of HIV. Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease.,Wang YF, Tie Y, Boross PI, Tozser J, Ghosh AK, Harrison RW, Weber IT J Med Chem. 2007 Sep 6;50(18):4509-15. Epub 2007 Aug 16. PMID:17696515 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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