3NU3

Wild Type HIV-1 Protease with Antiviral Drug Amprenavir

3NU3 の概要

• エントリーDOI: 10.2210/pdb3nu3/pdb
• 関連するPDBエントリー: 2IEN 3NU4 3NU5 3NU6 3NU9 3NUJ 3NUO
• 分子名称: Protease, SODIUM ION, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: enzyme inhibition, aspartic protease, hiv/aids, conformational change, amprenavir, hydrolase, 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): P03366
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22300.52

構造登録者

Wang, Y.-F.,Kovalevsky, A.Y.,Weber, I.T. (登録日: 2010-07-06, 公開日: 2010-08-25, 最終更新日: 2023-09-06)

主引用文献

Shen, C.H.,Wang, Y.F.,Kovalevsky, A.Y.,Harrison, R.W.,Weber, I.T.
Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters.
Febs J., 277:3699-3714, 2010

PubMed Abstract: The structural and kinetic effects of amprenavir (APV), a clinical HIV protease (PR) inhibitor, were analyzed with wild-type enzyme and mutants with single substitutions of V32I, I50V, I54V, I54M, I84V and L90M that are common in drug resistance. Crystal structures of the APV complexes at resolutions of 1.02-1.85 Å reveal the structural changes due to the mutations. Substitution of the larger side chains in PR(V32I) , PR(I54M) and PR(L90M) resulted in the formation of new hydrophobic contacts with flap residues, residues 79 and 80, and Asp25, respectively. Mutation to smaller side chains eliminated hydrophobic interactions in the PR(I50V) and PR(I54V) structures. The PR(I84V)-APV complex had lost hydrophobic contacts with APV, the PR(V32I)-APV complex showed increased hydrophobic contacts within the hydrophobic cluster and the PR(I50V) complex had weaker polar and hydrophobic interactions with APV. The observed structural changes in PR(I84V)-APV, PR(V32I)-APV and PR(I50V)-APV were related to their reduced inhibition by APV of six-, 10- and 30-fold, respectively, relative to wild-type PR. The APV complexes were compared with the corresponding saquinavir complexes. The PR dimers had distinct rearrangements of the flaps and 80's loops that adapt to the different P1' groups of the inhibitors, while maintaining contacts within the hydrophobic cluster. These small changes in the loops and weak internal interactions produce the different patterns of resistant mutations for the two drugs.

PubMed: 20695887
DOI: 10.1111/j.1742-4658.2010.07771.x

実験手法

X-RAY DIFFRACTION (1.02 Å)