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Literature summary extracted from

  • Gao, D.; Narasimhan, D.L.; Macdonald, J.; Brim, R.; Ko, M.C.; Landry, D.W.; Woods, J.H.; Sunahara, R.K.; Zhan, C.G.
    Thermostable variants of cocaine esterase for long-time protection against cocaine toxicity (2009), Mol. Pharmacol., 75, 318-323.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
3.1.1.84 medicine enhancing cocaine metabolism by administration of cocaine esterase (CocE) is a promising treatment strategy for cocaine overdose and addiction, because CocE is the most efficient native enzyme for metabolizing the naturally occurring cocaine. A major obstacle to the clinical application of CocE is the thermoinstability of native CocE with a half-life of only a few min at physiological temperature. Computational-experimental effort yields a CocE variant with a 30fold increase in plasma half-life both in vitro and in vivo Rhodococcus sp.

Protein Variants

EC Number Protein Variants Comment Organism
3.1.1.84 G173Q kcat and Km-value for cocaine is similar to wild-type value, half-life is increased 7fold compared to wild-type enzyme Rhodococcus sp.
3.1.1.84 additional information computational-experimental effort yields a CocE variant with a 30-fold increase in plasma half-life both in vitro and in vivo Rhodococcus sp.
3.1.1.84 T172R kcat and Km-value for cocaine is similar to wild-type value, half-life is increased 7fold compared to wild-type enzyme Rhodococcus sp.
3.1.1.84 T172R/G173Q kcat and Km-value for cocaine is similar to wild-type value, half-life is increased 30fold compared to wild-type enzyme Rhodococcus sp.

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
3.1.1.84 0.015
-
 cocaine ph 7.4, 37°C, mutant enzyme G173Q Rhodococcus sp.
3.1.1.84 0.021
-
 cocaine pH 7.4, 37°C, wild-type enzyme Rhodococcus sp.
3.1.1.84 0.024
-
 cocaine ph 7.4, 37°C, mutant enzyme T172R Rhodococcus sp.
3.1.1.84 0.024
-
 cocaine ph 7.4, 37°C, mutant enzyme T172R/G173Q Rhodococcus sp.

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.1.1.84 cocaine + H2O Rhodococcus sp. CocE is the most efficient native enzyme for metabolizing the naturally occurring cocaine ecgonine methyl ester + benzoate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.1.1.84 Rhodococcus sp. Q9L9D7
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
3.1.1.84
-
 Rhodococcus sp.

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.1.1.84 cocaine + H2O
-
 Rhodococcus sp. ecgonine methyl ester + benzoate
-
 ?
3.1.1.84 cocaine + H2O CocE is the most efficient native enzyme for metabolizing the naturally occurring cocaine Rhodococcus sp. ecgonine methyl ester + benzoate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.1.1.84 cocE
-
 Rhodococcus sp.

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.1.1.84 37
-
 assay at Rhodococcus sp.

Temperature Stability [°C]

EC Number Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
3.1.1.84 37
-
 half-life: 11 min (wild-type enzyme), 78 min (mutant enzyme T172R), 75 min (mutant enzyme G173Q), 305 min (mutant enzyme T172R/G173Q) Rhodococcus sp.

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
3.1.1.84 2247
-
 cocaine ph 7.4, 37°C, mutant enzyme T172R/G173Q Rhodococcus sp.
3.1.1.84 2323
-
 cocaine pH 7.4, 37°C, wild-type enzyme Rhodococcus sp.
3.1.1.84 2384
-
 cocaine ph 7.4, 37°C, mutant enzyme G173Q Rhodococcus sp.
3.1.1.84 2502
-
 cocaine ph 7.4, 37°C, mutant enzyme T172R Rhodococcus sp.

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.1.1.84 7.4
-
 assay at Rhodococcus sp.