2J9J

Atomic-resolution Crystal Structure of Chemically-Synthesized HIV-1 Protease Complexed with Inhibitor JG-365

2J9J の概要

• エントリーDOI: 10.2210/pdb2j9j/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000228
• 分子名称: PROTEASE, INHIBITOR MOLECULE JG365, SULFATE ION, ... (7 entities in total)
• 機能のキーワード: 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
• 由来する生物種: HUMAN IMMUNODEFICIENCY VIRUS 1; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 22855.72

構造登録者

Malito, E.,Shen, Y.,Johnson, E.C.B.,Tang, W.J. (登録日: 2006-11-11, 公開日: 2007-08-28, 最終更新日: 2023-12-13)

主引用文献

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

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: 17869270
DOI: 10.1016/J.JMB.2007.07.054

実験手法

X-RAY DIFFRACTION (1.04 Å)