title: The first examples of (S)-2-hydroxyacid dehydrogenases catalyzing the transfer of the pro-4S hydrogen of NADH are found in the archaea.
abstract: Reduction of 2-oxoacids to the corresponding (S)-2-hydroxyacids is an important transformation in biochemistry. To date all (S)-2-hydroxyacid dehydrogenases belonging to the L-lactate/L-malate dehydrogenase family have been found to transfer the pro-4R hydrogen of either NADH or NADPH to C-2 of the 2-oxoacid substrates during their reduction. Here, we report that recombinantly generated (S)-2-hydroxyacid dehydrogenases present in the methanoarchaea Methanococcus jannaschii and Methanothermus fervidus use the pro-4S hydrogen of NADH to reduce a series of 2-oxoacids to the corresponding (S)-2-hydroxyacids. This information as well as the low sequence identity between these archaeal enzymes and the L-lactate/L-malate family of enzymes indicate that these enzymes are not evolutionary related and therefore constitute a new class of (S)-2-hydroxyacid dehydrogenases.
authors.affiliation: Department of Biochemistry (0308), Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors.forename: M
authors.initials: M
authors.lastname: Graupner
authors.forename: R H
authors.initials: RH
authors.lastname: White
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D001105:Archaea / Q000201:enzymology*; D006859:Hydrogen / Q000737:chemistry / Q000378:metabolism; D024101:Mitochondrial Proteins; D009243:NAD / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D024101:Mitochondrial Proteins; D009243:NAD; D006859:Hydrogen; D000429:Alcohol Oxidoreductases; C083779:2-hydroxyacid dehydrogenase; C072878:hydroxyacid-oxoacid transhydrogenase