A Paradigm for Aldehyde Oxidation: Histidinol Dehydrogenase
Histidinol dehydrogenase (HDH, EC 188.8.131.52) catalyzes the oxidation of histidinol to histidine, using two moles of NAD. The reaction is the final step in the biosynthesis of histidine in bacteria, plants, and fungi. The enzyme is of particular interest in what it can tell us about dehydrogenase action: the reaction contains both alcohol and aldehyde dehydrogenase steps, apparently occurring at a single active site. Two other enzymes, UDP-glucose dehydrogenase (UDPGDH, EC 184.108.40.206) and hydroxymethyl glutaryl CoA reductase (HMGR, EC 220.127.116.11) catalyze conceptually similar 4-electron oxidations. Although the latter two have important roles in health and disease, for the enzymologist HDH offers the advantage of a long and interesting genetic history, and is particularly well suited to molecular approaches.
KeywordsTransition State Structure Hydride Transfer Uridine Diphosphate Glucose Single Active Site Histidine Operon
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- Cook, P. F.,&Bertagnolli, B. L. (1986) Kinetics of pyridine nucleotide-utilizing enzymes, in: Pyridine Nucleotide Coenzymes (Dolphin, D., Avramovic, O,&Poulsen, R., eds.) Part A, pp 405–447. Wiley, New York.Google Scholar
- Dutler, H., Ambar, A.,&Donatsch, J. (1986) Function of zinc in liver alcohol dehydrogenase, in: Zinc Enzymes (Bertini, I., Luchinat, C., Maret, W.,&Zeppezauer, M., eds.) Birkhauser, Boston, pp 471–483Google Scholar
- Grubmeyer, C. T., and Insinga, S. (1990) Histidinol dehydrogenase: 18O isotope shift in 13C NMR reveals origin of histidine oxygens. J. Am. Chem. Soc. (in press).Google Scholar
- Rogers, D. H., Panini, S. R., and Rudney, H. (1983) Properties of HMGCoA reductase and its mechanism of action, in: 3-Hydroxy-3-methylglutaryl CoA Reductase (Sabine, J. R., Ed.) pp 57–75, CRC PRess Cleveland.Google Scholar
- Scharschmidt, M., Fisher, M. A., and Cleland, W. W. (1984) Variation of transition state structure as a function of the nucleotide in reactions catalyzed by dehydrogenases. 1. Liver alcohol dehydrogenase with benzyl alcohol and yeast aldehyde dehydrogenase with benzaldehyde. Biochemistry 23, 5471–5478.PubMedCrossRefGoogle Scholar
- Yourno, J., and Ino, I. (1968) Purification and crystallization of histidinol dehydrogenase from Salmonella typhimuriumLT-2. J. Biol. Chem. 242, 3273–3276.Google Scholar