2j9j
From Proteopedia
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ATOMIC-RESOLUTION CRYSTAL STRUCTURE OF CHEMICALLY-SYNTHESIZED HIV-1 PROTEASE COMPLEXED WITH INHIBITOR JG-365
Overview
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.
About this Structure
2J9J is a Protein complex structure of sequences from Human immunodeficiency virus 1 with , and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
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
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