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Biochemistry. 2008 Dec 30;47(52):13745-53. doi: 10.1021/bi801994c.

Hydride transfer made easy in the reaction of alcohol oxidation catalyzed by flavin-dependent oxidases.

Author information

1
Departments of Chemistry and Biology, and The Center for Biotechnology and Drug Design, Georgia State University, Atlanta, Georgia 30302-4098, USA. ggadda@gsu.edu

Abstract

Choline oxidase (E.C. 1.1.3.17; choline-oxygen 1-oxidoreductase) catalyzes the two-step, four-electron oxidation of choline to glycine betaine with betaine aldehyde as enzyme-associated intermediate and molecular oxygen as final electron acceptor. Biochemical, structural, and mechanistic studies on the wild-type and a number of mutant forms of choline oxidase from Arthrobacter globiformis have recently been carried out, allowing for the delineation at molecular and atomic levels of the mechanism of alcohol oxidation catalyzed by the enzyme. First, the alcohol substrate is activated to its alkoxide species by the removal of the hydroxyl proton in the enzyme-substrate complex. The resulting activated alkoxide is correctly positioned for catalysis through electrostatic and hydrogen bonding interactions with a number of active site residues. After substrate activation and correct positioning are attained, alcohol oxidation occurs in a highly preorganized enzyme-substrate complex through quantum mechanical transfer of a hydride ion from the alpha-carbon of the chelated, alkoxide species to the N(5) atom of the enzyme-bound flavin. This mechanism in its essence is shared by another class of alcohol oxidizing enzymes that utilize a catalytic zinc to stabilize an alkoxide intermediate and NAD(P)(+) as the organic cofactor that accepts the hydride ion, whose paradigm example is alcohol dehydrogenase. It will be interesting to experimentally evaluate the attractive hypothesis of whether the mechanism of choline oxidase can be extended to other flavin-dependent enzymes as well as enzymes that utilize cofactors other than flavins in the oxidation of alcohols.

PMID:
19053234
DOI:
10.1021/bi801994c
[Indexed for MEDLINE]

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