InterPro domain: IPR016162

This superfamily represents a structural domain found at the N-terminal of aldehyde dehydrogenases [ 1 ]. These proteins contain two similar domains, each with a 3-layer alpha/beta/alpha structure, which probably arose from a duplication; this entry covers the N-terminal a/b/a domain. These enzymes binds NAD differently from other NAD(P)-dependent oxidoreductases.

Aldehyde dehydrogenases ( 1.2.1.3 and 1.2.1.5 ) are enzymes that oxidize a wide variety of aliphatic and aromatic aldehydes using NADP as a cofactor. In mammals at least four different forms of the enzyme are known [ 2 ]: class-1 (or Ald C) a tetrameric cytosolic enzyme, class-2 (or Ald M) a tetrameric mitochondrial enzyme, class- 3 (or Ald D) a dimeric cytosolic enzyme, and class IV a microsomal enzyme. Aldehyde dehydrogenases have also been sequenced from fungal and bacterial species. A number of enzymes are known to be evolutionary related to aldehyde dehydrogenases. A glutamic acid and a cysteine residue have been implicated in the catalytic activity of mammalian aldehyde dehydrogenase.

This domain superfamily is also found in gamma-glutamyl phosphate reductases, also known as glutamate-5-semialdehyde dehydrogenases.

1. Coenzyme isomerization is integral to catalysis in aldehyde dehydrogenase. Biochemistry 42, 7100-9
2. Inducible (class 3) aldehyde dehydrogenase from rat hepatocellular carcinoma and 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated liver: distant relationship to the class 1 and 2 enzymes from mammalian liver cytosol/mitochondria. Biochemistry 28, 1160-7