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Hydrolysis of organophosphate compounds by mutant butyrylcholinesterase: A story of two histidines by Moshe Amitay; Avital Shurki is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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## Abstract This study is aimed at understanding the hydrolysis mechanism of organophosphate (OP) compounds by G117H‐BChE. It is a theoretical study that focuses on the role of the G117H mutation in the dephosphorylation step. Various proposed mechanisms are examined. We show that His117 acts as a general base by activating a water molecule, and thus assisting its nucleophilic attack on the phosphate. The calculated reaction energy profile agrees well with the experimental data. Moreover, analysis of the reaction via its two hypothetical elementary steps, proton transfer and hydroxide attack, supports the role of His117 as a general base. Further support to the proposed mechanism is gained by structural comparison of the active site to RNAse A, which has similar composition of substrate and functional groups. The similarity between these enzymes extends beyond the structure and also becomes evident when comparing functionality of various active sites residues as well as rate–pH dependence obtained in the two cases. Moreover, it is demonstrated that an extended form of Bevilacqua's model (Biochemistry 2003;42:2259–2265) may resolve the apparent contradictions between the proposed me

Who reads Hydrolysis of organophosphate compounds by mutant butyrylcholinesterase: A story of two histidines?

Author

Moshe Amitay; Avital Shurki

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); Wiley-Liss Inc; Wiley (ISSN 0887-3585)

Published

2010

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)