1IIQ

CRYSTAL STRUCTURE OF HIV-1 PROTEASE COMPLEXED WITH A HYDROXYETHYLAMINE PEPTIDOMIMETIC INHIBITOR

1IIQ の概要

• エントリーDOI: 10.2210/pdb1iiq/pdb
• 関連するPDBエントリー: 1FQX
• 関連するBIRD辞書のPRD_ID: PRD_000384
• 分子名称: PROTEASE RETROPEPSIN, N-{(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl}-L-phenylalanyl-L-glutaminyl-L-phenylalaninamide, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: hiv protease, peptidomimetics, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human immunodeficiency virus 1
• 細胞内の位置: Gag-Pol polyprotein: Host cell membrane ; Lipid-anchor. Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P03367
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22770.82

構造登録者

Dohnalek, J.,Hasek, J.,Duskova, J.,Petrokova, H.,Hradilek, M.,Soucek, M.,Konvalinka, J.,Brynda, J.,Sedlacek, J.,Fabry, M. (登録日: 2001-04-24, 公開日: 2002-04-12, 最終更新日: 2024-03-13)

主引用文献

Dohnalek, J.,Hasek, J.,Duskova, J.,Petrokova, H.,Hradilek, M.,Soucek, M.,Konvalinka, J.,Brynda, J.,Sedlacek, J.,Fabry, M.
Hydroxyethylamine isostere of an HIV-1 protease inhibitor prefers its amine to the hydroxy group in binding to catalytic aspartates. A synchrotron study of HIV-1 protease in complex with a peptidomimetic inhibitor.
J.Med.Chem., 45:1432-1438, 2002

PubMed Abstract: A complex structure of HIV-1 protease with a hydroxyethylamine-containing inhibitor Boc-Phe-Psi[(S)-CH(OH)CH2NH]-Phe-Gln-Phe-NH2 has been determined by X-ray diffraction to 1.8 A resolution. The inhibitor is bound in the active site of the protease dimer with its hydroxyethylamine isostere participating in hydrogen bonds to the catalytic aspartates 25 and 25' and glycine 27' of the active site triads via five hydrogen bonds. The isostere amine interactions with the catalytic aspartates result in a displacement of the isostere hydroxy group in comparison with the common position known for analogous hydroxyethylamine containing inhibitors. A comparison with another inhibitor of this series shows that the change of one atom of the P2' side chain (Glu/Gln) leads to an altered ability of creating hydrogen bonds to the active site and within the inhibitor molecule. The diffraction data collected at a synchrotron radiation source enabled a detailed analysis of the complex solvation and of alternative conformations of protein side chains.

PubMed: 11906284
DOI: 10.1021/jm010979e

実験手法

X-RAY DIFFRACTION (1.83 Å)