2HB2

Structure of HIV protease 6X mutant in apo form

2HB2 の概要

• エントリーDOI: 10.2210/pdb2hb2/pdb
• 関連するPDBエントリー: 2AZC 2hb4 2hc0
• 分子名称: Protease (2 entities in total)
• 機能のキーワード: hiv, protease, retrovirus, aspartyl, hydrolase
• 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: 1
• 化学式量合計: 10749.71

構造登録者

Heaslet, H.,Tam, K.,Elder, J.H.,Stout, C.D. (登録日: 2006-06-13, 公開日: 2007-06-26, 最終更新日: 2024-02-14)

主引用文献

Heaslet, H.,Rosenfeld, R.,Giffin, M.,Lin, Y.C.,Tam, K.,Torbett, B.E.,Elder, J.H.,McRee, D.E.,Stout, C.D.
Conformational flexibility in the flap domains of ligand-free HIV protease.
Acta Crystallogr.,Sect.D, 63:866-875, 2007

PubMed Abstract: The crystal structures of wild-type HIV protease (HIV PR) in the absence of substrate or inhibitor in two related crystal forms at 1.4 and 2.15 A resolution are reported. In one crystal form HIV PR adopts an 'open' conformation with a 7.7 A separation between the tips of the flaps in the homodimer. In the other crystal form the tips of the flaps are 'curled' towards the 80s loop, forming contacts across the local twofold axis. The 2.3 A resolution crystal structure of a sixfold mutant of HIV PR in the absence of substrate or inhibitor is also reported. The mutant HIV PR, which evolved in response to treatment with the potent inhibitor TL-3, contains six point mutations relative to the wild-type enzyme (L24I, M46I, F53L, L63P, V77I, V82A). In this structure the flaps also adopt a 'curled' conformation, but are separated and not in contact. Comparison of the apo structures to those with TL-3 bound demonstrates the extent of conformational change induced by inhibitor binding, which includes reorganization of the packing between twofold-related flaps. Further comparison with six other apo HIV PR structures reveals that the 'open' and 'curled' conformations define two distinct families in HIV PR. These conformational states include hinge motion of residues at either end of the flaps, opening and closing the entire beta-loop, and translational motion of the flap normal to the dimer twofold axis and relative to the 80s loop. The alternate conformations also entail changes in the beta-turn at the tip of the flap. These observations provide insight into the plasticity of the flap domains, the nature of their motions and their critical role in binding substrates and inhibitors.

PubMed: 17642513
DOI: 10.1107/S0907444907029125

実験手法

X-RAY DIFFRACTION (2.3 Å)