Yang_2010_Chem.Biol.Interact_187_148

Reference

Title : Characterization of a high-activity mutant of human butyrylcholinesterase against (-)-cocaine - Yang_2010_Chem.Biol.Interact_187_148
Author(s) : Yang W , Xue L , Fang L , Chen X , Zhan CG
Ref : Chemico-Biological Interactions , 187 :148 , 2010
Abstract : Cocaine addiction and overdose are a well-known public health problem. There is no approved medication available for cocaine abuse treatment. Our recently designed and discovered high-activity mutant (A199S/S287G/A328W/Y332G) of human butyrylcholinesterase (BChE) has been recognized to be worth exploring for clinical application in humans as a potential anti-cocaine medication. The catalytic rate constant (k(cat)) and Michaelis-Menten constant (K(M)) for (-)-cocaine hydrolysis catalyzed by A199S/S287G/A328W/Y332G BChE (without fusion with any other peptide) have been determined to be 3,060 min(-1) and 3.1 microM, respectively, in the present study. The determined kinetic parameters reveal that the un-fused A199S/S287G/A328W/Y332G mutant has a approximately 1,080-fold improved catalytic efficiency (k(cat)/K(M)) against (-)-cocaine compared to the wild-type BChE. The approximately 1,080-fold improvement in the catalytic efficiency of the un-fused A199S/S287G/A328W/Y332G mutant is very close to the previously reported the approximately 1,000-fold improvement in the catalytic efficiency of the A199S/S287G/A328W/Y332G mutant fused with human serum albumin. These results suggest that the albumin fusion did not significantly change the catalytic efficiency of the BChE mutant while extending the plasma half-life. In addition, we have also examined the catalytic activities of the A199S/S287G/A328W/Y332G mutant against two other substrates, acetylthiocholine (ATC) and butyrylthiocholine (BTC). It has been shown that the A199S/S287G/A328W/Y332G mutations actually decreased the catalytic efficiencies of BChE against ATC and BTC, while considerably improving the catalytic efficiency of BChE against (-)-cocaine.
ESTHER : Yang_2010_Chem.Biol.Interact_187_148
PubMedSearch : Yang_2010_Chem.Biol.Interact_187_148
PubMedID: 20060817

Related information

Citations formats

Yang W, Xue L, Fang L, Chen X, Zhan CG (2010)
Characterization of a high-activity mutant of human butyrylcholinesterase against (-)-cocaine
Chemico-Biological Interactions 187 :148

Yang W, Xue L, Fang L, Chen X, Zhan CG (2010)
Chemico-Biological Interactions 187 :148

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    [paper] => Yang_2010_Chem.Biol.Interact_187_148
    [author] => Yang W || Xue L || Fang L || Chen X || Zhan CG
    [year] => 2010
    [title] => Characterization of a high-activity mutant of human butyrylcholinesterase against (-)-cocaine
    [journal] => Chemico-Biological Interactions
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    [page] => 148
    [medline] => 20060817
    [abstract] => Yang_2010_Chem.Biol.Interact_187_148
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            [longtext] => Yang_2010_Chem.Biol.Interact_187_148
            [content] => Cocaine addiction and overdose are a well-known public health problem. There is no approved medication available for cocaine abuse treatment. Our recently designed and discovered high-activity mutant (A199S/S287G/A328W/Y332G) of human butyrylcholinesterase (BChE) has been recognized to be worth exploring for clinical application in humans as a potential anti-cocaine medication. The catalytic rate constant (k(cat)) and Michaelis-Menten constant (K(M)) for (-)-cocaine hydrolysis catalyzed by A199S/S287G/A328W/Y332G BChE (without fusion with any other peptide) have been determined to be 3,060 min(-1) and 3.1 microM, respectively, in the present study. The determined kinetic parameters reveal that the un-fused A199S/S287G/A328W/Y332G mutant has a approximately 1,080-fold improved catalytic efficiency (k(cat)/K(M)) against (-)-cocaine compared to the wild-type BChE. The approximately 1,080-fold improvement in the catalytic efficiency of the un-fused A199S/S287G/A328W/Y332G mutant is very close to the previously reported the approximately 1,000-fold improvement in the catalytic efficiency of the A199S/S287G/A328W/Y332G mutant fused with human serum albumin. These results suggest that the albumin fusion did not significantly change the catalytic efficiency of the BChE mutant while extending the plasma half-life. In addition, we have also examined the catalytic activities of the A199S/S287G/A328W/Y332G mutant against two other substrates, acetylthiocholine (ATC) and butyrylthiocholine (BTC). It has been shown that the A199S/S287G/A328W/Y332G mutations actually decreased the catalytic efficiencies of BChE against ATC and BTC, while considerably improving the catalytic efficiency of BChE against (-)-cocaine.
        )

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