2f8g | pdb_00002f8g

HIV-1 protease mutant I50V complexed with inhibitor TMC114

spinqualitylabelsall models 2f8g, resolution 1.22Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2f8g 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: 017, ACY, CL, GOL, NA Related: 2f80, 2f81 Gene: POL (Human immunodeficiency virus 1) 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 TMC-114 (UIC-94017) of HIV-1 protease (PR) has been studied with three PR variants containing single mutations D30N, I50V, and L90M, which provide resistance to the major clinical inhibitors. The inhibition constants (K(i)) of TMC-114 for mutants PR(D30N), PR(I50V), and PR(L90M) were 30-, 9-, and 0.14-fold, respectively, relative to wild-type PR. The molecular basis for the inhibition was analyzed using high-resolution (1.22-1.45 A) crystal structures of PR mutant complexes with TMC-114. In PR(D30N), the inhibitor has a water-mediated interaction with the side chain of Asn30 rather than the direct interaction observed in PR, which is consistent with the relative inhibition. Similarly, in PR(I50V) the inhibitor loses favorable hydrophobic interactions with the side chain of Val50. TMC-114 has additional van der Waals contacts in PR(L90M) structure compared to the PR structure, leading to a tighter binding of the inhibitor. The observed changes in PR structure and activity are discussed in relation to the potential for development of resistant mutants on exposure to TMC-114. Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M.,Kovalevsky AY, Tie Y, Liu F, Boross PI, Wang YF, Leshchenko S, Ghosh AK, Harrison RW, Weber IT J Med Chem. 2006 Feb 23;49(4):1379-87. PMID:16480273 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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