3OUC

MDR769 HIV-1 protease complexed with p2/NC hepta-peptide

3OUC の概要

• エントリーDOI: 10.2210/pdb3ouc/pdb
• 関連するPDBエントリー: 3OTS 3OTY 3OU1 3OU3 3OU4 3OUA 3OUB 3OUD
• 分子名称: MDR HIV-1 protease, p2/NC substrate peptide (3 entities in total)
• 機能のキーワード: mdr hiv-1 protease, inhibitor, drug resistance, substrate envelope, hiv-1 protease, protease, p2/nc substrate peptide, none, hydrolase, hydrolase-peptide complex, hydrolase/peptide
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• 細胞内の位置: Matrix protein p17: Virion (By similarity): Q9YP46
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 22376.31

構造登録者

Liu, Z.,Wang, Y.,Brunzelle, J.,Kovari, I.A.,Kovari, L.C. (登録日: 2010-09-14, 公開日: 2011-03-30, 最終更新日: 2024-02-21)

主引用文献

Liu, Z.,Wang, Y.,Brunzelle, J.,Kovari, I.A.,Kovari, L.C.
Nine Crystal Structures Determine the Substrate Envelope of the MDR HIV-1 Protease.
Protein J., 30:173-183, 2011

PubMed Abstract: Under drug selection pressure, emerging mutations render HIV-1 protease drug resistant, leading to the therapy failure in anti-HIV treatment. It is known that nine substrate cleavage site peptides bind to wild type (WT) HIV-1 protease in a conserved pattern. However, how the multidrug-resistant (MDR) HIV-1 protease binds to the substrate cleavage site peptides is yet to be determined. MDR769 HIV-1 protease (resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, and 90) was selected for present study to understand the binding to its natural substrates. MDR769 HIV-1 protease was co-crystallized with nine substrate cleavage site hepta-peptides. Crystallographic studies show that MDR769 HIV-1 protease has an expanded substrate envelope with wide open flaps. Furthermore, ligand binding energy calculations indicate weaker binding in MDR769 HIV-1 protease-substrate complexes. These results help in designing the next generation of HIV-1 protease inhibitors by targeting the MDR HIV-1 protease.

PubMed: 21394574
DOI: 10.1007/s10930-011-9316-2

実験手法

X-RAY DIFFRACTION (2 Å)