Properties of Intermediates in the Catalytic Cycle of Oxalate Oxidoreductase and Its Suicide Inactivation by Pyruvate

Biochemistry
Elizabeth PierceStephen W Ragsdale

Abstract

Oxalate:ferredoxin oxidoreductase (OOR) is an unusual member of the thiamine pyrophosphate (TPP)-dependent 2-oxoacid:ferredoxin oxidoreductase (OFOR) family in that it catalyzes the coenzyme A (CoA)-independent conversion of oxalate into 2 equivalents of carbon dioxide. This reaction is surprising because binding of CoA to the acyl-TPP intermediate of other OFORs results in formation of a CoA ester, and in the case of pyruvate:ferredoxin oxidoreductase (PFOR), CoA binding generates the central metabolic intermediate acetyl-CoA and promotes a 10(5)-fold acceleration of the rate of electron transfer. Here we describe kinetic, spectroscopic, and computational results to show that CoA has no effect on catalysis by OOR and describe the chemical rationale for why this cofactor is unnecessary in this enzymatic transformation. Our results demonstrate that, like PFOR, OOR binds pyruvate and catalyzes decarboxylation to form the same hydroxyethylidine-TPP (HE-TPP) intermediate and one-electron transfer to generate the HE-TPP radical. However, in OOR, this intermediate remains stranded at the active site as a covalent inhibitor. These and other results indicate that, like other OFOR family members, OOR generates an oxalate-derived adduct ...Continue Reading

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Citations

May 23, 2018·The Journal of Biological Chemistry·Alicia A DeColliCaren L Freel Meyers
Mar 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Percival Yang-Ting ChenCatherine L Drennan
May 14, 2019·Joule·Percival Yang-Ting ChenSean J Elliott

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Methods Mentioned

BETA
X-ray

Software Mentioned

Gaussian

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