1M0B

HIV-1 protease in complex with an ethyleneamine inhibitor

1M0B の概要

• エントリーDOI: 10.2210/pdb1m0b/pdb
• 関連するPDBエントリー: 1FQX 1IIQ 1LZQ
• 関連するBIRD辞書のPRD_ID: PRD_000383
• 分子名称: PROTEASE RETROPEPSIN, N-{(3S)-3-[(tert-butoxycarbonyl)amino]-4-phenylbutyl}-L-phenylalanyl-L-alpha-glutamyl-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: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P03367
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22387.43

構造登録者

Petrokova, H.,Hasek, J.,Dohnalek, J. (登録日: 2002-06-12, 公開日: 2004-01-13, 最終更新日: 2024-02-14)

主引用文献

Petrokova, H.,Duskova, J.,Dohnalek, J.,Skalova, T.,Vondrackova-Buchtelova, E.,Soucek, M.,Konvalinka, J.,Brynda, J.,Fabry, M.,Sedlacek, J.,Hasek, J.
Role of hydroxyl group and R/S configuration of isostere in binding properties of HIV-1 protease inhibitors
Eur.J.Biochem., 271:4451-4461, 2004

PubMed Abstract: The crystal structure of the complex between human immunodeficiency virus type 1 (HIV-1) protease and a peptidomimetic inhibitor of ethyleneamine type has been refined to R factor of 0.178 with diffraction limit 2.5 A. The peptidomimetic inhibitor Boc-Phe-Psi[CH2CH2NH]-Phe-Glu-Phe-NH2 (denoted here as OE) contains the ethyleneamine replacement of the scissile peptide bond. The inhibitor lacks the hydroxyl group which is believed to mimic tetrahedral transition state of proteolytic reaction and thus is suspected to be necessary for good properties of peptidomimetic HIV-1 protease inhibitors. Despite the missing hydroxyl group the inhibition constant of OE is 1.53 nm and it remains in the nanomolar range also towards several available mutants of HIV-1 protease. The inhibitor was found in the active site of protease in an extended conformation with a unique hydrogen bond pattern different from hydroxyethylene and hydroxyethylamine inhibitors. The isostere nitrogen forms a hydrogen bond to one catalytic aspartate only. The other aspartate forms two weak hydrogen bridges to the ethylene group of the isostere. A comparison with other inhibitors of this series containing isostere hydroxyl group in R or S configuration shows different ways of accommodation of inhibitor in the active site. Special attention is devoted to intermolecular contacts between neighbouring dimers responsible for mutual protein adhesion and for a special conformation of Met46 and Phe53 side chains not expected for free protein in water solution.

PubMed: 15560786
DOI: 10.1111/j.1432-1033.2004.04384.x

実験手法

X-RAY DIFFRACTION (2.45 Å)