1SDT

Crystal structures of HIV protease V82A and L90M mutants reveal changes in indinavir binding site.

1SDT の概要

• エントリーDOI: 10.2210/pdb1sdt/pdb
• 関連するPDBエントリー: 1FF0 1SDU 1SDV
• 分子名称: protease RETROPEPSIN, CHLORIDE ION, N-[2(R)-HYDROXY-1(S)-INDANYL]-5-[(2(S)-TERTIARY BUTYLAMINOCARBONYL)-4(3-PYRIDYLMETHYL)PIPERAZINO]-4(S)-HYDROXY-2(R)-PHENYLMETHYLPENTANAMIDE, ... (4 entities in total)
• 機能のキーワード: drug resistance; hiv-1, hydrolase
• 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: 22166.05

構造登録者

Mahalingam, B.,Wang, Y.-F.,Boross, P.I.,Tozser, J.,Louis, J.M.,Harrison, R.W.,Weber, I.T. (登録日: 2004-02-14, 公開日: 2004-05-25, 最終更新日: 2023-08-23)

主引用文献

Mahalingam, B.,Wang, Y.-F.,Boross, P.I.,Tozser, J.,Louis, J.M.,Harrison, R.W.,Weber, I.T.
Crystal structures of HIV protease V82A and L90M mutants reveal changes in the indinavir-binding site
Eur.J.Biochem., 271:1516-1524, 2004

PubMed Abstract: The crystal structures of the wild-type HIV-1 protease (PR) and the two resistant variants, PR(V82A) and PR(L90M), have been determined in complex with the antiviral drug, indinavir, to gain insight into the molecular basis of drug resistance. V82A and L90M correspond to an active site mutation and nonactive site mutation, respectively. The inhibition (K(i)) of PR(V82A) and PR(L90M) was 3.3- and 0.16-fold, respectively, relative to the value for PR. They showed only a modest decrease, of 10-15%, in their k(cat)/K(m) values relative to PR. The crystal structures were refined to resolutions of 1.25-1.4 A to reveal critical features associated with inhibitor resistance. PR(V82A) showed local changes in residues 81-82 at the site of the mutation, while PR(L90M) showed local changes near Met90 and an additional interaction with indinavir. These structural differences concur with the kinetic data.

PubMed: 15066177
DOI: 10.1111/j.1432-1033.2004.04060.x

実験手法

X-RAY DIFFRACTION (1.3 Å)