Binding of histidinal to histidinol dehydrogenase

Abstract

One molecule of the enzymatic intermediate histidinal is firmly bound per subunit of histidinol dehydrogenase (EC 1.1.1.23) and protected against decomposition. The dissociation rate constant of the histidinal–histidinol dehydrogenase complex is estimated as 2.5 × 10–5 S–1. Steady‐state kinetic measurements studying the oxidation of histidinol to histidine and the reduction of histidinal to histidinol allow to calculate the association rate constants for histidinal. For both reactions the association rate constant is found as 1.9 × 106 M–1 S–1. Thus the dissociation constant of the histidinal–histidinol dehydrogenase complex is estimated to be of the order of 1.4 × 10–11 M.

Mechanism of Salmonella typhimurium Histidinol Dehydrogenase: Kinetic Isotope Effects and pH Profiles

“…Adams (1) observed that the presence of aldehyde-derivitizing reagents did not affect overall catalysis by HDH and suggested that histidinal, the proposed intermediate, did not dissociate from the active site during overall catalysis. Go ¨risch and Ho ¨lke (7) verified that externally added histidinal was bound very tightly to HDH (see also ref 8) and was protected from alkaline degradation. These results led to the hypothesis that enzyme-bound histidinal exists as an adduct with an enzymic nucleophile.…”

Histidine biosynthesis, its regulation and biotechnological application in Corynebacterium glutamicum

“…l ‐Histidinol is first oxidized by histidinol dehydrogenase to l ‐histidinal, which is further oxidized to l ‐histidine (Alifano et al ., ). Both steps are catalysed by the same enzyme to prevent the decomposition of the unstable l ‐histidinal intermediate (Görisch and Hölke, ) and two molecules NAD + (oxidized nicotinamide adenine dinucleotide) are reduced during the reaction (Adams, ). The native HisD enzyme from S. typhimurium (HisD St ) acts as a homodimer and both subunits are linked by disulfide bridges (Eccleston et al ., ).…”

Zinc metalloenzymes as new targets against the bacterial pathogen Brucella

“…L-HDH is essential for macrophagic replication as the enzyme involved in the final 2 steps of the 10 step histidine biosynthesis pathway [28]. This catalyzed reaction from histidinol to histidine occurs through the sequential reduction of two molecules of NAD [29] (Scheme 1) via the highly stable histidinal-enzyme intermediate [30] in a BiUniUniBiPingPong mechanism [31].…”