This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is L-histidinol:NAD+ oxidoreductase. This enzyme is also called L-histidinol dehydrogenase.
Histidinol is held inside the active site thanks to a zinc ion, but the zinc ion does not participate in the catalysis otherwise. The zinc ion is held in place by His262, Gln259, Asp360 and His419 (which, in homodimeric histidinol dehydrogenases, comes from the other monomer). Histidinol itself is held in place by His327 and His367 from one moment unit and Glu414 from the other monomer unit.[3]
A Cys residue has been implicated in the catalytic mechanism of the second oxidative step.[4] However, according to newer studies with histidinol dehydrogenase from E. coli, the mechanism is catalyzed by four bases, B1-B4. His327 acts as the first base, deprotonating histidinol's hydroxyl group. Concomitantly, hydride is abstracted from histidinol by NAD+, which is then exchanged for a second NAD+ molecule. Glu325 acts as the second base, deprotonating a molecule of water, which then attacks histidinol. At the same time, His327 (now protonated) donates a proton to the aldehydic oxygen, which results in a gem-diol. After then, His327 again deprotonates one of the hydroxyl groups and NAD+ abstracts a proton from the reactive carbon atom. This series of steps oxidizes the hydroxyl group to a carboxylic acid.[3]
^ abcdGrubmeyer CT, Gray WR (August 1986). "A cysteine residue (cysteine-116) in the histidinol binding site of histidinol dehydrogenase". Biochemistry. 25 (17): 4778–84. doi:10.1021/bi00365a009. PMID3533140.