7F65

Bacetrial Cocaine Esterase with mutations T172R/G173Q/V116K/S117A/A51L, bound to benzoic acid

7F65 の概要

• エントリーDOI: 10.2210/pdb7f65/pdb
• 分子名称: Cocaine esterase, SULFATE ION, BENZOIC ACID, ... (4 entities in total)
• 機能のキーワード: cocaine esterase, mutantions, benzoylecgonine metabolism, hydrolase
• 由来する生物種: Rhodococcus sp. MB1 'Bresler 1999'
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 62584.83

構造登録者

Ouyang, P.F.,Zhang, Y.,Tong, J. (登録日: 2021-06-24, 公開日: 2021-09-15, 最終更新日: 2023-11-29)

主引用文献

Chen, X.,Deng, X.,Zhang, Y.,Wu, Y.,Yang, K.,Li, Q.,Wang, J.,Yao, W.,Tong, J.,Xie, T.,Hou, S.,Yao, J.
Computational Design and Crystal Structure of a Highly Efficient Benzoylecgonine Hydrolase.
Angew.Chem.Int.Ed.Engl., 60:21959-21965, 2021

PubMed Abstract: Benzoylecgonine (BZE) is the major toxic metabolite of cocaine and is responsible for the long-term cocaine-induced toxicity owing to its long residence time in humans. BZE is also the main contaminant following cocaine consumption. Here, we identified the bacterial cocaine esterase (CocE) as a BZE-metabolizing enzyme (BZEase), which can degrade BZE into biological inactive metabolites (ecgonine and benzoic acid). CocE was redesigned by a reactant-state-based enzyme design theory. An encouraging mutant denoted as BZEase2, presented a >400-fold improved catalytic efficiency against BZE compared with wild-type (WT) CocE. In vivo, a single dose of BZEase2 (1 mg kg , IV) could eliminate nearly all BZE within only two minutes, suggesting the enzyme has the potential for cocaine overdose treatment and BZE elimination in the environment by accelerating BZE clearance. The crystal structure of a designed BZEase was also determined.

PubMed: 34351032
DOI: 10.1002/anie.202108559

実験手法

X-RAY DIFFRACTION (2.202 Å)