Fumarate reductase: structural and mechanistic insights from the catalytic reduction of 2-methylfumarate.

Caroline Wardrope, Christopher G Mowat, Malcolm D Walkinshaw, Graeme A Reid, Stephen K Chapman

Index: FEBS Lett. 580(6) , 1677-80, (2006)

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Abstract

The soluble fumarate reductase (FR) from Shewanella frigidimarina can catalyse the reduction of 2-methylfumarate with a k(cat) of 9.0 s(-1) and a K(M) of 32 microM. This produces the chiral molecule 2-methylsuccinate. Here, we present the structure of FR to a resolution of 1.5 A with 2-methylfumarate bound at the active site. The mode of binding of 2-methylfumarate allows us to predict the stereochemistry of the product as (S)-2-methylsuccinate. To test this prediction we have analysed the product stereochemistry by circular dichroism spectroscopy and confirmed the production of (S)-2-methylsuccinate.