2j9k

Atomic-resolution Crystal Structure of Chemically-Synthesized HIV-1 Protease Complexed with Inhibitor MVT-101

spinqualitylabelsall models 2j9k, resolution 1.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2j9k is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 2NC, ACT, GOL, SO4 NonStd Res: ABA, NLE, SLZ Related: 2j9j 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 The human immunodeficiency virus 1 (HIV-1) protease (PR) is an aspartyl protease essential for HIV-1 viral infectivity. HIV-1 PR has one catalytic site formed by the homodimeric enzyme. We chemically synthesized fully active HIV-1 PR using modern ligation methods. When complexed with the classic substrate-derived inhibitors JG-365 and MVT-101, the synthetic HIV-1 PR formed crystals that diffracted to 1.04- and 1.2-A resolution, respectively. These atomic-resolution structures revealed additional structural details of the HIV-1 PR's interactions with its active site ligands. Heptapeptide inhibitor JG-365, which has a hydroxyethylamine moiety in place of the scissile bond, binds in two equivalent antiparallel orientations within the catalytic groove, whereas the reduced isostere hexapeptide MVT-101 binds in a single orientation. When JG-365 was converted into the natural peptide substrate for molecular dynamic simulations, we found putative catalytically competent reactant states for both lytic water and direct nucleophilic attack mechanisms. Moreover, free energy perturbation calculations indicated that the insertion of catalytic water into the catalytic site is an energetically favorable process. Insights from atomic-resolution X-ray structures of chemically synthesized HIV-1 protease in complex with inhibitors.,Johnson EC, Malito E, Shen Y, Pentelute B, Rich D, Florian J, Tang WJ, Kent SB J Mol Biol. 2007 Oct 26;373(3):573-86. Epub 2007 Aug 2. PMID:17869270 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Immunodeficiency virus protease 3D structures Integrase

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