2j9k: Difference between revisions

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.

2J9K is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with SO4, ACT, ACE, NH2 and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2J9K OCA].  

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