Sandbox Reserved 987: Difference between revisions
From Proteopedia
Jump to navigationJump to search
David Buck (talk | contribs) No edit summary |
David Buck (talk | contribs) No edit summary |
||
| Line 36: | Line 36: | ||
== Mutations == | == Mutations == | ||
The wild-type cocaine esterase is not stable at physiological temperature, which poses a problem for its use as a pharmaceutical drug. Mutations have been conducted in order to increase its thermostability. In vivo testing showed the wild-type having a 11 min half-life. A mutant having its threonine swapped for a arginine at position 172 was found to last 9 times as long, and a mutant that further had its glycine swapped for a glutamine was found to last 24 times as long (~ | The wild-type cocaine esterase is not stable at physiological temperature, which poses a problem for its use as a pharmaceutical drug. Mutations have been conducted in order to increase its thermostability. In vivo testing showed the wild-type having a 11 min half-life. A mutant having its threonine swapped for a arginine at position 172 (T172R) was found to last 9 times as long, and a mutant that further had its glycine swapped for a glutamine (T172R/G173Q) was found to last 24 times as long (~4h 20m)<sup><ref>Gao D., Narasimhan D. L., Macdonald J., Brim R., Ko M., Landry D. W., Woods J. H., Sunahara R. K., Zhan C. (2009) Thermostable variants of cocaine esterase for long-time protection against cocaine toxicity. Mol. Pharmacol. 75, 318-323.</ref></sup> Another mutant that has been explored is the L169K/G173Q mutant. This showed an in vivo half life of ~2h 20m.<sup><ref>Brim R. L., Nance M. R., Youngstrom D. W., Narasimhan D., Zhan C. G., Tesmer J. J. G., Sunahara, R. K., Woods J. W. (2010) A Thermally Stable Form of Bacterial Cocaine Esterase: A Potential Therapeutic Agent for Treatment of Cocaine Abuse. Mol. Pharmacol. 77(4), 593-600.</ref></sup> | ||
== Medical Relevance == | == Medical Relevance == | ||
