1NH0

1.03 A structure of HIV-1 protease: inhibitor binding inside and outside the active site

1NH0 の概要

• エントリーDOI: 10.2210/pdb1nh0/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000401
• 分子名称: PROTEASE RETROPEPSIN, peptidomimetic inhibitor KI2-PHE-GLU-GLU-NH2, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: aspartyl protease, human immunodeficiency virus, inhibitor design, 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: 4
• 化学式量合計: 23421.42

構造登録者

Brynda, J.,Rezacova, P.,Fabry, M.,Horejsi, M.,Hradilek, M.,Soucek, M.,Konvalinka, J.,Sedlacek, J. (登録日: 2002-12-18, 公開日: 2004-04-13, 最終更新日: 2023-08-16)

主引用文献

Brynda, J.,Rezacova, P.,Fabry, M.,Horejsi, M.,Stouracova, R.,Sedlacek, J.,Soucek, M.,Hradilek, M.,Lepsik, M.,Konvalinka, J.
A Phenylnorstatine Inhibitor Binding to HIV-1 Protease: Geometry, Protonation, and Subsite-Pocket Interactions Analyzed at Atomic Resolution
J.Med.Chem., 47:2030-2036, 2004

PubMed Abstract: The X-ray structure of a complex of HIV-1 protease (PR) with a phenylnorstatine inhibitor Z-Pns-Phe-Glu-Glu-NH(2) has been determined at 1.03 A, the highest resolution so far reported for any HIV PR complex. The inhibitor shows subnanomolar K(i) values for both the wild-type PR and the variant representing one of the most common mutations linked to resistance development. The structure comprising the phenylnorstatine moiety of (2R,3S)-chirality displays a unique pattern of hydrogen bonding to the two catalytic aspartate residues. This high resolution makes it possible to assess the donor and acceptor relations of this hydrogen bonding and to indicate a proton shared by the two catalytic residues. A structural mechanism for the unimpaired inhibition of the protease Val82Ala mutant is also suggested, based on energy calculations and analyses.

PubMed: 15056001
DOI: 10.1021/jm031105q

実験手法

X-RAY DIFFRACTION (1.03 Å)