2J9J
Atomic-resolution Crystal Structure of Chemically-Synthesized HIV-1 Protease Complexed with Inhibitor JG-365
Summary for 2J9J
| Entry DOI | 10.2210/pdb2j9j/pdb |
| Related PRD ID | PRD_000228 |
| Descriptor | PROTEASE, INHIBITOR MOLECULE JG365, SULFATE ION, ... (7 entities in total) |
| Functional Keywords | hydrolase-hydrolase inhibitor complex, protease, hydrolase, high resolution, rna-directed dna polymerase, aspartyl protease, human immunodeficiency virus 1, hydrolase- hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | HUMAN IMMUNODEFICIENCY VIRUS 1 More |
| Total number of polymer chains | 3 |
| Total formula weight | 22855.72 |
| Authors | Malito, E.,Shen, Y.,Johnson, E.C.B.,Tang, W.J. (deposition date: 2006-11-11, release date: 2007-08-28, Last modification date: 2023-12-13) |
| Primary citation | Johnson, E.C.B.,Malito, E.,Shen, Y.,Pentelute, B.,Rich, D.,Florian, J.,Tang, W.J.,Kent, S.B.H. Insights from Atomic-Resolution X-Ray Structures of Chemically Synthesized HIV-1 Protease in Complex with Inhibitors. J.Mol.Biol., 373:573-, 2007 Cited by PubMed Abstract: 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. PubMed: 17869270DOI: 10.1016/J.JMB.2007.07.054 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.04 Å) |
Structure validation
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