4U7V

Structure of wild-type HIV protease in complex with degraded photosensitive inhibitor

4U7V の概要

• エントリーDOI: 10.2210/pdb4u7v/pdb
• 関連するPDBエントリー: 4U7Q
• 分子名称: V-1 protease, BETA-MERCAPTOETHANOL, N-[(2S,4S,5S)-4-hydroxy-1,6-diphenyl-5-{[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}hexan-2-yl]-L-valinamide, ... (4 entities in total)
• 機能のキーワード: hiv-1, viral protease, aspartic protease, inhibition, hydrolase
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22290.56

構造登録者

Pachl, P.,Rezacova, P.,Schimer, J. (登録日: 2014-07-31, 公開日: 2015-03-25, 最終更新日: 2023-12-20)

主引用文献

Schimer, J.,Pavova, M.,Anders, M.,Pachl, P.,Sacha, P.,Cigler, P.,Weber, J.,Majer, P.,Rezacova, P.,Krausslich, H.G.,Muller, B.,Konvalinka, J.
Triggering HIV polyprotein processing by light using rapid photodegradation of a tight-binding protease inhibitor.
Nat Commun, 6:6461-6461, 2015

PubMed Abstract: HIV protease (PR) is required for proteolytic maturation in the late phase of HIV replication and represents a prime therapeutic target. The regulation and kinetics of viral polyprotein processing and maturation are currently not understood in detail. Here we design, synthesize, validate and apply a potent, photodegradable HIV PR inhibitor to achieve synchronized induction of proteolysis. The compound exhibits subnanomolar inhibition in vitro. Its photolabile moiety is released on light irradiation, reducing the inhibitory potential by 4 orders of magnitude. We determine the structure of the PR-inhibitor complex, analyze its photolytic products, and show that the enzymatic activity of inhibited PR can be fully restored on inhibitor photolysis. We also demonstrate that proteolysis of immature HIV particles produced in the presence of the inhibitor can be rapidly triggered by light enabling thus to analyze the timing, regulation and spatial requirements of viral processing in real time.

PubMed: 25751579
DOI: 10.1038/ncomms7461

実験手法

X-RAY DIFFRACTION (1.38 Å)