Putative D-isomer specific 2-hydroxyacid dehydrogenases, NAD-binding and catalytic domains
2-Hydroxyacid dehydrogenases 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/glycerate and related dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily include groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-adenosylhomocysteine hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. While many members of this family are dimeric, alanine DH is hexameric and phosphoglycerate DH is tetrameric.
Feature 1: catalytic site [active site], 3 residue positions
Conserved feature residue pattern:R [QE] H
Evidence:
Comment:canonical triad of the FDH-like active center is an R[EQ]H motif
Comment:conserved Arg H-bonds with the substrate carboxylate; conserved histidine H-bonded to the carboxylic acid forms an acid-base catalyst for a proton shuttle with the 2-hydroxyl moiety of the substrate
Jiyao W et al.(2023). "The conserved domain database in 2023.",