Alcohol dehydrogenase (1.1.1.1) (ADH) catalyzes the reversible oxidation ofalcohols to their corresponding acetaldehyde or ketone with the concomitant reduction of NAD:alcohol + NAD = aldehyde or ketone + NADHCurrently three structurally and catalytically different types of alcoholdehydrogenases are known:
- Zinc-containing 'long-chain' alcohol dehydrogenases.
- Insect-type, or 'short-chain' alcohol dehydrogenases.
- Iron-containing alcohol dehydrogenases.
Zinc-containing ADH's [
1,
2] are dimeric or tetrameric enzymes that bind twoatoms of zinc per subunit. One of the zinc atom is essential for catalyticactivity while the other is not. Both zinc atoms are coordinated by eithercysteine or histidine residues; the catalytic zinc is coordinated by twocysteines and one histidine. Zinc-containing ADH's are found in bacteria,mammals, plants, and in fungi. In many species there is more than one isozyme(for example, humans have at least six isozymes, yeast have three, etc.). Anumber of other zinc-dependent dehydrogenases are closely related to zincADH [
3] and are included in this family.
In addition, this family includes NADP-dependent quinone oxidoreductase (1.6.5.5),an enzyme found in bacteria (gene qor), in yeast and in mammals where, in somespecies such as rodents, it has been recruited as an eye lens protein and isknown as zeta-crystallin [4]. The sequence of quinone oxidoreductase isdistantly related to that other zinc-containing alcohol dehydrogenases and itlacks the zinc-ligand residues. The torpedo fish and mammalian synaptic vesiclemembrane protein vat-1 is related to qor.
This entry represents the cofactor-binding domain of these enzymes, which is normally found towards the C terminus. Structural studies indicate that it forms a classical Rossman fold that reversibly binds NAD(H) [5, 6, 7].
1. Characteristics of alcohol/polyol dehydrogenases. The zinc-containing long-chain alcohol dehydrogenases. Eur. J. Biochem. 167, 195-201
2. Progressive sequence alignment and molecular evolution of the Zn-containing alcohol dehydrogenase family. J. Mol. Evol. 34, 522-35
3. Dual relationships of xylitol and alcohol dehydrogenases in families of two protein types. FEBS Lett. 324, 9-14
4. Zeta-crystallin versus other members of the alcohol dehydrogenase super-family. Variability as a functional characteristic. FEBS Lett. 322, 240-4
5. X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase. Structure 11, 1071-85
6. Amino acid residues in the nicotinamide binding site contribute to catalysis by horse liver alcohol dehydrogenase. Biochemistry 42, 2907-15
7. Crystal structure of Escherichia coli QOR quinone oxidoreductase complexed with NADPH. J. Mol. Biol. 249, 785-99
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