7f65
Bacetrial Cocaine Esterase with mutations T172R/G173Q/V116K/S117A/A51L, bound to benzoic acidBacetrial Cocaine Esterase with mutations T172R/G173Q/V116K/S117A/A51L, bound to benzoic acid
Structural highlights
FunctionCOCE_RHOSM Hydrolyzes cocaine to benzoate and ecgonine methyl ester, endowing the bacteria with the ability to utilize cocaine as a sole source of carbon and energy for growth, as this bacterium lives in the rhizosphere of coca plants. Also efficiently hydrolyzes cocaethylene, a more potent cocaine metabolite that has been observed in patients who concurrently abuse cocaine and alcohol. Is able to prevent cocaine-induced convulsions and lethality in rat.[1] [2] [3] Publication Abstract from PubMedBenzoylecgonine (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(-1) , 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. Computational Design and Crystal Structure of a Highly Efficient Benzoylecgonine Hydrolase.,Chen X, Deng X, Zhang Y, Wu Y, Yang K, Li Q, Wang J, Yao W, Tong J, Xie T, Hou S, Yao J Angew Chem Int Ed Engl. 2021 Aug 5. doi: 10.1002/anie.202108559. PMID:34351032[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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