Background: NADPH-dependent ␣-keto acid reductase, belonging to the short-chain dehydrogenase/reductase family, is involved in bacterial alginate metabolism. Results: A novel NADH-dependent ␣-keto acid reductase was identified, and its tertiary structure was determined by x-ray crystallography. Conclusion: Two short and long loops are structural determinants for coenzyme specificity. Significance: A method for structure-based conversion of a coenzyme requirement was established.