7F65
Bacetrial Cocaine Esterase with mutations T172R/G173Q/V116K/S117A/A51L, bound to benzoic acid
Summary for 7F65
Entry DOI | 10.2210/pdb7f65/pdb |
Descriptor | Cocaine esterase, SULFATE ION, BENZOIC ACID, ... (4 entities in total) |
Functional Keywords | cocaine esterase, mutantions, benzoylecgonine metabolism, hydrolase |
Biological source | Rhodococcus sp. MB1 'Bresler 1999' |
Total number of polymer chains | 1 |
Total formula weight | 62584.83 |
Authors | Ouyang, P.F.,Zhang, Y.,Tong, J. (deposition date: 2021-06-24, release date: 2021-09-15, Last modification date: 2023-11-29) |
Primary citation | 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 Cited by 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: 34351032DOI: 10.1002/anie.202108559 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.202 Å) |
Structure validation
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