InterPro domain: IPR011548

3-hydroxyisobutyrate dehydrogenase is an enzyme that catalyzes the NAD+-dependent oxidation of 3-hydroxyisobutyrate to methylmalonate semialdehyde of the valine catabolism pathway.

In Pseudomonas aeruginosa, 3-hydroxyisobutyrate dehydrogenase (mmsB) is co-induced with methylmalonate-semialdehyde dehydrogenase (mmsA) when grown on medium containing valine as the sole carbon source. The positive transcriptional regulator of this operon (mmsR) is located upstream of these genes and has been identified as a member of the XylS/AraC family of transcriptional regulators [ 1 ].

3-hydroxyisobutyrate dehydrogenase shares high sequence homology to the characterised 3-hydroxyisobutyrate dehydrogenase from rat liver [ 2 ] with conservation of proposed NAD+ binding residues at the N terminus (G-8,10,13,24 and D-31).

This enzyme belongs to the 3-hydroxyacid dehydrogenase family, sharing a common evolutionary origin and enzymatic mechanism with 6-phosphogluconate [ 3 ]. HIBADH exhibits sequence similarity to the NAD binding domain of 6-phosphogluconate dehydrogenase.

1. Characterization of the mmsAB operon of Pseudomonas aeruginosa PAO encoding methylmalonate-semialdehyde dehydrogenase and 3-hydroxyisobutyrate dehydrogenase. J. Biol. Chem. 267, 13585-92
2. Cloning and sequence analysis of a cDNA for 3-hydroxyisobutyrate dehydrogenase. Evidence for its evolutionary relationship to other pyridine nucleotide-dependent dehydrogenases. J. Biol. Chem. 264, 5899-903
3. Structural and mechanistic similarities of 6-phosphogluconate and 3-hydroxyisobutyrate dehydrogenases reveal a new enzyme family, the 3-hydroxyacid dehydrogenases. FEBS Lett. 389, 263-7