Homologous Superfamily

Aldehyde/histidinol dehydrogenase (IPR016161)

Short name: Ald_DH/histidinol_DH

Overlapping entries



This entry represents a structural domain found in aldehyde dehydrogenases [PMID: 12795606] and histidinol dehydrogenases [PMID: 11842181]. These proteins contain two similar domains, each with a 3-layer alpha/beta/alpha structure, which probably arose from a duplication. These enzymes bind NAD differently from other NAD(P)-dependent oxidoreductases.

Aldehyde dehydrogenases (EC: and EC: 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 [PMID: 2713359]: 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.

Histidinol dehydrogenase (EC: (HDH) catalyses the terminal step in the biosynthesis of histidine in bacteria, fungi, and plants, the four-electron oxidation of L-histidinol to histidine. In 4-electron dehydrogenases, a single active site catalyses 2 separate oxidation steps: oxidation of the substrate alcohol to an intermediate aldehyde; and oxidation of the aldehyde to the product acid, in this case His [PMID: 3533140]. The reaction proceeds via a tightly- or covalently-bound inter-mediate, and requires the presence of 2 NAD molecules [PMID: 3533140]. By contrast with most dehydrogenases, the substrate is bound before the NAD coenzyme [PMID: 3533140]. A Cys residue has been implicated in the catalytic mechanism of the second oxidative step [PMID: 3533140]. In bacteria HDH is a single chain polypeptide; in fungi it is the C-terminal domain of a multifunctional enzyme which catalyzes three different steps of histidine biosynthesis; and in plants it is expressed as nuclear encoded protein precursor which is exported to the chloroplast [PMID: 2034659].

GO terms

Biological Process

GO:0055114 oxidation-reduction process

Molecular Function

GO:0016491 oxidoreductase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.