2B7F

Crystal structure of human T-cell leukemia virus protease, a novel target for anti-cancer design

2B7F の概要

• エントリーDOI: 10.2210/pdb2b7f/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000429
• 分子名称: HTLV protease, (ACE)APQV(STA)VMHP peptide, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human T-lymphotropic virus 1
• 細胞内の位置: Matrix protein p19: Virion . Capsid protein p24: Virion . Nucleocapsid protein p15-pro: Virion : P10274
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 78776.32

構造登録者

Li, M.,Laco, G.S.,Jaskolski, M.,Rozycki, J.,Alexandratos, J.,Wlodawer, A.,Gustchina, A. (登録日: 2005-10-04, 公開日: 2005-12-06, 最終更新日: 2025-11-12)

主引用文献

Li, M.,Laco, G.S.,Jaskolski, M.,Rozycki, J.,Alexandratos, J.,Wlodawer, A.,Gustchina, A.
Crystal structure of human T cell leukemia virus protease, a novel target for anticancer drug design
Proc.Natl.Acad.Sci.Usa, 102:18332-18337, 2005

PubMed Abstract: The successful development of a number of HIV-1 protease (PR) inhibitors for the treatment of AIDS has validated the utilization of retroviral PRs as drug targets and necessitated their detailed structural study. Here we report the structure of a complex of human T cell leukemia virus type 1 (HTLV-1) PR with a substrate-based inhibitor bound in subsites P5 through P5'. Although HTLV-1 PR exhibits an overall fold similar to other retroviral PRs, significant structural differences are present in several loop areas, which include the functionally important flaps, previously considered to be structurally highly conserved. Potential key residues responsible for the resistance of HTLV-1 PR to anti-HIV drugs are identified. We expect that the knowledge accumulated during the development of anti-HIV drugs, particularly in overcoming drug resistance, will help in designing a novel class of antileukemia drugs targeting HTLV-1 PR and in predicting their drug-resistance profile. The structure presented here can be used as a starting point for the development of such anticancer therapies.

PubMed: 16352712
DOI: 10.1073/pnas.0509335102

実験手法

X-RAY DIFFRACTION (2.6 Å)