<p>This entry represents a structural domain found in aldehyde dehydrogenases [<cite idref="PUB00022295"/>] and histidinol dehydrogenases [<cite idref="PUB00016238"/>]. 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. </p><p>Aldehyde dehydrogenases (<db_xref db="EC" dbkey="1.2.1.3"/> and <db_xref db="EC" dbkey="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 [<cite idref="PUB00000303"/>]: 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.</p><p>Histidinol dehydrogenase (<db_xref db="EC" dbkey="1.1.1.23"/>) (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 [<cite idref="PUB00000285"/>]. The reaction proceeds via a tightly- or covalently-bound inter-mediate, and requires the presence of 2 NAD molecules [<cite idref="PUB00000285"/>]. By contrast with most dehydrogenases, the substrate is bound before the NAD coenzyme [<cite idref="PUB00000285"/>]. A Cys residue has been implicated in the catalytic mechanism of the second oxidative step [<cite idref="PUB00000285"/>]. 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 [<cite idref="PUB00004740"/>].</p> Aldehyde/histidinol dehydrogenase