InterPro: IPR001692 Histidinol dehydrogenase, conserved site

Histidinol dehydrogenase (EC: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 [1]. The reaction proceeds via a tightly- or covalently-bound inter-mediate, and requires the presence of 2 NAD molecules [1]. By contrast with most dehydrogenases, the substrate is bound before the NAD coenzyme [1]. A Cys residue has been implicated in the catalytic mechanism of the second oxidative step [1].

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 [2].