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The chloride cocaine esterase (EC 3.1.1.84, CocE, hCE2, hCE-2, human carboxylesterase 2; systematic name cocaine benzoylhydrolase)[1][2][3][4][5] catalyses the reaction
cocaine + H2O ecgonine methyl ester + benzoate
Rhodococcus sp. strain MB1 and Pseudomonas maltophilia strain MB11L can utilize cocaine as sole source of carbon and energy.
The theoretical molecular mass is 62,128 Da.[6] This enzyme and redesigned versions of it have been studied as a potential treatment for cocaine addiction in humans.[7]
TNX-1300 (T172R/G173Q double-mutant cocaine esterase 200 mg, i.v. solution)[8] is being developed under an Investigational New Drug application (IND) for the treatment of cocaine intoxication.[9] TNX-1300 (formerly known as RBP-8000) is a recombinant protein enzyme produced through rDNA technology in a non-disease-producing strain of E. coli bacteria. Cocaine Esterase (CocE) was identified in bacteria (Rhodococcus) that use cocaine as its sole source of carbon and nitrogen and that grow in soil surrounding coca plants.[10] The gene encoding CocE was identified and the protein was extensively characterized.[1][4][10][11] CoCE catalyzes the breakdown of cocaine into metabolite ecgonine methyl ester and benzoic acid. Wild-type CocE is unstable at body temperature, so targeted mutations were introduced in the CocE gene and resulted in the T172R/G173Q Double-Mutant CocE, which is active for approximately 6 hours at body temperature.[1] In a Phase 2 study, TNX-1300 at 100 mg or 200 mg i.v. doses was well tolerated and interrupted cocaine effects after cocaine 50 mg i.v. challenge.[9]
The enzyme is important in bioremediation, levels of cocaine in European ocean water were cited at 20 ng/L, similar levels in which swollen muscles, and in some cases broken muscle fibers of eels were reported in a controlled study.[12]
^Bresler MM, Rosser SJ, Basran A, Bruce NC (March 2000). "Gene cloning and nucleotide sequencing and properties of a cocaine esterase from Rhodococcus sp. strain MB1". Applied and Environmental Microbiology. 66 (3): 904–8. Bibcode:2000ApEnM..66..904B. doi:10.1128/aem.66.3.904-908.2000. PMC 91920. PMID 10698749.
^Britt AJ, Bruce NC, Lowe CR (April 1992). "Identification of a cocaine esterase in a strain of Pseudomonas maltophilia". Journal of Bacteriology. 174 (7): 2087–94. doi:10.1128/jb.174.7.2087-2094.1992. PMC 205824. PMID 1551831.
^ abLarsen NA, Turner JM, Stevens J, Rosser SJ, Basran A, Lerner RA, Bruce NC, Wilson IA (January 2002). "Crystal structure of a bacterial cocaine esterase". Nature Structural Biology. 9 (1): 17–21. doi:10.1038/nsb742. PMID 11742345. S2CID 847034.
^Pindel EV, Kedishvili NY, Abraham TL, Brzezinski MR, Zhang J, Dean RA, Bosron WF (June 1997). "Purification and cloning of a broad substrate specificity human liver carboxylesterase that catalyzes the hydrolysis of cocaine and heroin". The Journal of Biological Chemistry. 272 (23): 14769–75. doi:10.1074/jbc.272.23.14769. PMID 9169443.
^Bresler, Matthew M.; Rosser, Susan J.; Basran, Amrik; Bruce, Neil C. (March 2000). "Gene Cloning and Nucleotide Sequencing and Properties of a Cocaine Esterase from Rhodococcus sp. Strain MB1". Applied and Environmental Microbiology. 66 (3): 904–908. Bibcode:2000ApEnM..66..904B. doi:10.1128/AEM.66.3.904-908.2000. ISSN 0099-2240. PMC 91920. PMID 10698749.
^Narasimhan D, Woods JH, Sunahara RK (February 2012). "Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction". Future Medicinal Chemistry. 4 (2): 137–50. doi:10.4155/fmc.11.194. PMC 3290992. PMID 22300094.
^"Tonix boosts pipeline with Columbia University-developed cocaine intoxication drug". FierceBiotech. Retrieved 2019-05-28.
^ abNasser, Azmi F.; Fudala, Paul J.; Zheng, Bo; Liu, Yongzhen; Heidbreder, Christian (2014-10-02). "A Randomized, Double-Blind, Placebo-Controlled Trial of RBP-8000 in Cocaine Abusers: Pharmacokinetic Profile of RBP-8000 and Cocaine and Effects of RBP-8000 on Cocaine-Induced Physiological Effects". Journal of Addictive Diseases. 33 (4): 289–302. doi:10.1080/10550887.2014.969603. ISSN 1055-0887. PMID 25299069. S2CID 8417112.
^ abBresler, M. M.; Rosser, S. J.; Basran, A.; Bruce, N. C. (2000). "Gene cloning and nucleotide sequencing and properties of a cocaine esterase from Rhodococcus sp. strain MB1". Applied and Environmental Microbiology. 66 (3): 904–908. Bibcode:2000ApEnM..66..904B. doi:10.1128/aem.66.3.904-908.2000. ISSN 0099-2240. PMC 91920. PMID 10698749.
^Turner, James M.; Larsen, Nicholas A.; Basran, Amrik; Barbas, Carlos F.; Bruce, Neil C.; Wilson, Ian A.; Lerner, Richard A. (2002-10-15). "Biochemical characterization and structural analysis of a highly proficient cocaine esterase". Biochemistry. 41 (41): 12297–12307. doi:10.1021/bi026131p. ISSN 0006-2960. PMID 12369817.
^"European eels found to suffer muscle damage due to cocaine in the water".
asset, TNX-1300 (T172R/G173Q double-mutant cocaineesterase 200 mg, i.v. solution), for the treatment of cocaine intoxication. TNX-1300 (formerly known as...
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Populations of Coffea arabica in the Montane Rainforests of Ethiopia" Cocaineesterase, an enzyme This disambiguation page lists articles associated with...
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CES1 gene. The protein is also historically known as serine esterase 1 (SES1), monocyte esterase and cholesterol ester hydrolase (CEH). Three transcript variants...
surgeon Heinrich Braun. Prior to the discovery of amylocaine and procaine, cocaine was a commonly used local anesthetic. Einhorn wished his new discovery...
histamine H1 Receptor knockout mice coincide with changes in acetylcholine esterase activity in the hippocampus and dopamine turnover in the cerebellum". Neuroscience...
Mu opioid. IV. Protein binding = 70%; hydrolysed by blood and tissue esterases; half-life = 20 min; excretion = urine (95%). Anaesthesia maintenance...
a variety of different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more or less...
a half-life of approximately one minute. It is rapidly inactivated by esterases. It was approved by the United States Food and Drug Administration on...
responsible for the hydrolysis of ester- and amide-bond-containing drugs such as cocaine and heroin. They also hydrolyze long-chain fatty acid esters and thioesters...
trichloroethanol and trichloroethanol glucuronide by erythrocytes and plasma esterases and into trichloroacetic acid in 4 to 5 days. It has a very narrow therapeutic...
linkage which undergoes rapid hydrolysis by non-specific tissue and plasma esterases. This means that accumulation does not occur with remifentanil and its...
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"Catalog of 680 variations among eight cytochrome p450 ( CYP) genes, nine esterase genes, and two other genes in the Japanese population". Journal of Human...
(1997). "Enzyme Models Based on Molecularly Imprinted Polymers with Strong Esterase Activity". Angewandte Chemie International Edition in English. 36 (18):...
short-lived owing to digestion by esterases. From procaine Mautz synthesized procainamide, which is not a substrate for esterases. Procainamide has the additional...
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