InterPro: IPR010061 Methylmalonate-semialdehyde dehydrogenase

These proteins are involved in valine catabolism, methylmalonate-semialdehyde dehydrogenase catalyses the irreversible NAD+- and CoA-dependent oxidative decarboxylation of methylmalonate semialdehyde to propionyl-CoA. Methylmalonate-semialdehyde dehydrogenase has been characterised in both prokaryotes [1, 2] and eukaryotes [3], functioning as a mammalian tetramer and a bacterial homodimer. Although similar in monomeric molecular mass and enzymatic activity, the N-terminal sequence in Pseudomonas aeruginosa does not correspond with the N-terminal sequence predicted for rat liver. Sequence homology to a variety of prokaryotic and eukaryotic aldehyde dehydrogenases places MMSDH in the aldehyde dehydrogenase (NAD+) superfamily making MMSDH's CoA requirement unique among known ALDHs. Methylmalonate semialdehyde dehydrogenase is closely related to betaine aldehyde dehydrogenase, 2-hydroxymuconic semialdehyde dehydrogenase, and class 1 and 2 aldehyde dehydrogenase [3].

In Bacillus, a highly homologous protein to methylmalonic acid semialdehyde dehydrogenase, groups out from the main MMSDH clade with Listeria and Sulfolobus. This Bacillus protein has been suggested to be located in an iol operon and/or involved in myo-inositol catabolism, converting malonic semialdehyde to acetyl CoA ad CO2 [4]. The preceding enzymes responsible for valine catabolism are present in Bacillus, Listeria, and Sulfolobus.