Insights into the Mechanism of Flavoprotein-catalyzed Amine Oxidation from Nitrogen Isotope Effects on the Reaction of N-methyltryptophan Oxidase

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2007 Jun 5

PMID 17542620

Citations 28

Authors

Erik C Ralph

Jennifer S Hirschi

Mark A Anderson

W Wallace Cleland

Daniel A Singleton

Paul F Fitzpatrick

Affiliations

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Abstract

The mechanism of N-methyltryptophan oxidase, a flavin-dependent amine oxidase from Escherichia coli, was studied using a combination of kinetic isotope effects and theoretical calculations. The 15(kcat/Km) kinetic isotope effect for sarcosine oxidation is pH-dependent with a limiting value of 0.994-0.995 at high pH. Density functional theory calculations on model systems were used to interpret these isotope effects. The isotope effects are inconsistent with proposed mechanisms involving covalent amine-flavin adducts but cannot by themselves conclusively distinguish between some discrete electron-transfer mechanisms and a direct hydride-transfer mechanism, although the latter mechanism is more consistent with the energetics of the reaction.

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