Formate/glycerate dehydrogenases, D-specific 2-hydroxy acid dehydrogenases and related dehydrogenases
The formate/glycerate dehydrogenase like family contains a diverse group of enzymes such as formate dehydrogenase (FDH), glycerate dehydrogenase (GDH), D-lactate dehydrogenase, L-alanine dehydrogenase, and S-Adenosylhomocysteine hydrolase, that share a common 2-domain structure. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar domains of the alpha/beta Rossmann fold NAD+ binding form. The NAD(P) binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD(P) is bound, primarily to the C-terminal portion of the 2nd (internal) domain. While many members of this family are dimeric, alanine DH is hexameric and phosphoglycerate DH is tetrameric. 2-hydroxyacid dehydrogenases are enzymes that catalyze the conversion of a wide variety of D-2-hydroxy acids to their corresponding keto acids. The general mechanism is (R)-lactate + acceptor to pyruvate + reduced acceptor. Formate dehydrogenase (FDH) catalyzes the NAD+-dependent oxidation of formate ion to carbon dioxide with the concomitant reduction of NAD+ to NADH. FDHs of this family contain no metal ions or prosthetic groups. Catalysis occurs though direct transfer of a hydride ion to NAD+ without the stages of acid-base catalysis typically found in related dehydrogenases.
Jiyao W et al.(2023). "The conserved domain database in 2023.",