9K48

Bacetrial Cocaine Esterase with mutations T172R/G173Q/V116K/S117A/A51K

Summary for 9K48

• Entry DOI: 10.2210/pdb9k48/pdb
• Descriptor: Cocaine esterase, BENZOIC ACID (3 entities in total)
• Functional Keywords: cocaine esterase, be specificity, hydrolase
• Biological source: Rhodococcus sp. (strain MB1 Bresler)
• Total number of polymer chains: 1
• Total formula weight: 62504.79

Authors

Zhang, Y.,Tong, J.S. (deposition date: 2024-10-21, release date: 2024-12-18)

Primary citation

Chen, X.,Zhang, Y.,Tong, J.,Ouyang, P.,Deng, X.,Zhang, J.,Liu, H.,Hu, Y.,Yao, W.,Wang, J.,Wang, X.,Hou, S.,Yao, J.
Catalytic mechanism, computational design, and crystal structure of a highly specific and efficient benzoylecgonine hydrolase.
Int.J.Biol.Macromol., 283:137767-137767, 2024

PubMed Abstract: Enzyme therapy for cocaine detoxification should break down both cocaine and its primary toxic metabolite, benzoylecgonine (BZE), which is also the main form of cocaine contaminant in the environment. An ideal BZE-metabolizing enzyme (BZEase) is expected to be highly efficient and selective in BZE hydrolysis. Here, BZEase4 was engineered from bacterial cocaine esterase (CocE) by our reactant state-based enzyme design theories (RED), which has a 34,977-fold improved substrate discrimination between BZE and the neurotransmitter acetylcholine (ACh), compared with wild-type CocE. Under the physiological concentrations of BZE and ACh, the reaction velocity of BZEase4 against BZE is 2.25 × 10-fold higher than it against ACh, suggesting BZEase4 has extremely high substrate selectivity for BZE over ACh to minimize the potential cholinergic side-effects. This study provides additional evidence supporting the further development of BZEase4 toward a promising therapeutic for cocaine overdose, a potentially effective and eco-friendly enzymatic method for BZE degradation in the environment.

PubMed: 39561846
DOI: 10.1016/j.ijbiomac.2024.137767

Experimental method

X-RAY DIFFRACTION (2.249 Å)