Biology:Cocaine esterase

From HandWiki
Short description: Class of enzymes
Identifiers
EC number3.1.1.84
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum

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 [math]\displaystyle{ \rightleftharpoons }[/math] 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]

References

  1. ↑ 1.0 1.1 1.2 "Thermostable variants of cocaine esterase for long-time protection against cocaine toxicity". Molecular Pharmacology 75 (2): 318–23. February 2009. doi:10.1124/mol.108.049486. PMID 18987161. 
  2. ↑ "Gene cloning and nucleotide sequencing and properties of a cocaine esterase from Rhodococcus sp. strain MB1". Applied and Environmental Microbiology 66 (3): 904–8. March 2000. doi:10.1128/aem.66.3.904-908.2000. PMID 10698749. 
  3. ↑ "Identification of a cocaine esterase in a strain of Pseudomonas maltophilia". Journal of Bacteriology 174 (7): 2087–94. April 1992. doi:10.1128/jb.174.7.2087-2094.1992. PMID 1551831. 
  4. ↑ 4.0 4.1 "Crystal structure of a bacterial cocaine esterase". Nature Structural Biology 9 (1): 17–21. January 2002. doi:10.1038/nsb742. PMID 11742345. 
  5. ↑ "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. June 1997. doi:10.1074/jbc.272.23.14769. PMID 9169443. 
  6. ↑ 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. doi:10.1128/AEM.66.3.904-908.2000. ISSN 0099-2240. PMID 10698749. 
  7. ↑ "Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction". Future Medicinal Chemistry 4 (2): 137–50. February 2012. doi:10.4155/fmc.11.194. PMID 22300094. 
  8. ↑ "Tonix boosts pipeline with Columbia University-developed cocaine intoxication drug" (in en). https://www.fiercebiotech.com/biotech/tonix-boosts-pipeline-columbia-university-developed-cocaine-intoxication-med. 
  9. ↑ 9.0 9.1 Nasser, 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" (in en). Journal of Addictive Diseases 33 (4): 289–302. doi:10.1080/10550887.2014.969603. ISSN 1055-0887. PMID 25299069. 
  10. ↑ 10.0 10.1 Bresler, 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. doi:10.1128/aem.66.3.904-908.2000. ISSN 0099-2240. PMID 10698749. 
  11. ↑ 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. 
  12. ↑ "European eels found to suffer muscle damage due to cocaine in the water". https://phys.org/news/2018-06-european-eels-muscle-due-cocaine.html. 

External links



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:Cocaine_esterase&oldid=3545140"