Kinetic characterization of an efficient cocaine hydrolase against toxic metabolites of cocaine

M Zhan, S Hou, L Shang, X Chen, CG Zhan… - Organic & Biomolecular …, 2023 - pubs.rsc.org
In the presence of alcohol, cocaine metabolism produces a number of metabolites, including
three toxic ones (cocaethylene, norcocaine, and norcocaethylene) which are all more toxic …

Catalytic activities of cocaine hydrolases against the most toxic cocaine metabolite norcocaethylene

X Zheng, X Chen, T Zhang, M Zhan, CG Zhan… - Organic & …, 2020 - pubs.rsc.org
A majority of cocaine users also consume alcohol. The concurrent use of cocaine and
alcohol produces the pharmacologically active metabolites cocaethylene and …

Catalytic activities of a highly efficient cocaine hydrolase for hydrolysis of biologically active cocaine metabolites norcocaine and benzoylecgonine

L Shang, Z Jin, H Wei, S Park, CG Zhan, F Zheng - Scientific Reports, 2023 - nature.com
Cocaine is a widely abused, hepatotoxic drug without an FDA-approved pharmacotherapy
specific for cocaine addiction or overdose. It is recognized as a promising therapeutic …

Reaction pathway and free energy profile for cocaine hydrolase-catalyzed hydrolysis of (−)-cocaine

J Liu, CG Zhan - Journal of chemical theory and computation, 2012 - ACS Publications
The reaction pathway of (−)-cocaine hydrolysis catalyzed by our recently discovered, most
efficient cocaine hydrolase, which is the A199S/F227A/S287G/A328W/Y332G mutant of …

Toward cocaine esterase therapeutics

CJ Rogers, JM Mee, GF Kaufmann… - Journal of the …, 2005 - ACS Publications
Cocaine is among the most reinforcing of all drugs of abuse, yet no effective
pharmacotherapy is available. Herein, we report the development and characterization of …

Reaction mechanism for cocaine esterase-catalyzed hydrolyses of (+)-and (−)-cocaine: unexpected common rate-determining step

J Liu, X Zhao, W Yang, CG Zhan - The Journal of Physical …, 2011 - ACS Publications
First-principles quantum mechanical/molecular mechanical free energy calculations have
been performed to examine the catalytic mechanism for cocaine esterase (CocE)-catalyzed …

Catalytic reaction mechanism for drug metabolism in human carboxylesterase-1: cocaine hydrolysis pathway

J Yao, X Chen, F Zheng, CG Zhan - Molecular pharmaceutics, 2018 - ACS Publications
Carboxylesterase-1 (CE-1) is a crucial enzyme responsible for metabolism/activation/
inactivation of xenobiotics (therapeutic agents, prodrugs, abused drugs, and …

Human carboxylesterase 2 in cocaine metabolism

PR Figueiredo, RD González, ATP Carvalho - Molecular Catalysis, 2021 - Elsevier
Increased hydrolysis of cocaine to nontoxic compounds is a promising way to prevent
cocaine-induced toxicity. However, the short half-life of cocaine in the blood and the rapid …

Clinical potential of an enzyme-based novel therapy for cocaine overdose

T Zhang, X Zheng, Z Zhou, X Chen, Z Jin, J Deng… - Scientific Reports, 2017 - nature.com
It is a grand challenge to develop a truly effective medication for treatment of cocaine
overdose. The current available, practical emergence treatment for cocaine overdose …

Fundamental reaction mechanism and free energy profile for (−)-cocaine hydrolysis catalyzed by cocaine esterase

J Liu, A Hamza, CG Zhan - Journal of the American Chemical …, 2009 - ACS Publications
The fundamental reaction mechanism of cocaine esterase (CocE)-catalyzed hydrolysis of (−)-
cocaine and the corresponding free energy profile have been studied by performing …