InterPro domain: IPR033689

NAD-dependent formate dehydrogenase (FDH) catalyzes the NAD+-dependent oxidation of a formate anion to carbon dioxide coupled with the reduction of NAD+ to NADH. Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxy acid dehydrogenase family have 2 highly similar subdomains of the alpha/beta form, with NAD binding occurring in the cleft between subdomains. NAD contacts are primarily to the Rossmann-fold NAD-binding domain which is inserted within the linear sequence of the more diverse flavodoxin-like catalytic subdomain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. FDHs of this family contain no metal ions or prosthetic groups. Catalysis occurs though direct transfer of the hydride ion to NAD+ without the stages of acid-base catalysis typically found in related dehydrogenases. FDHs are found in all methylotrophic microorganisms in energy production from C1 compounds such as methanol, and in the stress responses of plants [ 1 , 2 , 3 ]. NAD-dependent FDH is useful in cofactor regeneration in asymmetrical biocatalytic reduction processes, where FDH irreversibly oxidizes formate to carbon dioxide, while reducing the oxidized form of the cofactor to the reduced form.

1. Expression cassettes for formaldehyde and fluoroacetate resistance, two dominant markers in Saccharomyces cerevisiae. Yeast 13, 551-9
2. Engineering of coenzyme specificity of formate dehydrogenase from Saccharomyces cerevisiae. Biochem. J. 367, 841-7
3. Functional analysis of structural genes for NAD(+)-dependent formate dehydrogenase in Saccharomyces cerevisiae. Yeast 19, 509-20