D
IPR013149

Alcohol dehydrogenase-like, C-terminal

InterPro entry
Short nameADH-like_C
Overlapping
homologous
superfamilies
 

Description

Alcohol dehydrogenase (
1.1.1.1
) (ADH) catalyses the reversible oxidation of alcohols to their corresponding acetaldehyde or ketone with the concomitant reduction of NAD:

alcohol + NAD = aldehyde or ketone + NADH

Currently three structurally and catalytically different types of alcohol dehydrogenases are known:

     * Zinc-containing 'long-chain' alcohol dehydrogenases.
     * Insect-type, or 'short-chain' alcohol dehydrogenases.
     * Iron-containing alcohol dehydrogenases.

Zinc-containing ADH's
[4, 5]
are dimeric or tetrameric enzymes that bind two atoms of zinc per subunit. One of the zinc atoms is essential for catalytic activity while the other is not. Both zinc atoms are coordinated by either cysteine or histidine residues; the catalytic zinc is coordinated by two cysteines 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.). A number of other zinc-dependent dehydrogenases are closely related to zinc ADH
[6]
and are included in this family:


 * Sorbitol dehydrogenase (
1.1.1.14
)
 * L-threonine 3-dehydrogenase (
1.1.1.103
)
 * Glutathione-dependent formaldehyde dehydrogenase (
1.1.1.284
)
 * Mannitol dehydrogenase (
1.1.1.255
)


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 some species such as rodents, it has been recruited as an eye lens protein and is known as zeta-crystallin
[7]
. The sequence of quinone oxidoreductase is distantly related to that other zinc-containing alcohol dehydrogenases and it lacks the zinc-ligand residues. The torpedo fish and mammalian synaptic vesicle membrane 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)
[1, 2, 3]
.

References

1.X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase. Pauly TA, Ekstrom JL, Beebe DA, Chrunyk B, Cunningham D, Griffor M, Kamath A, Lee SE, Madura R, Mcguire D, Subashi T, Wasilko D, Watts P, Mylari BL, Oates PJ, Adams PD, Rath VL. Structure 11, 1071-85, (2003). View articlePMID: 12962626

2.Amino acid residues in the nicotinamide binding site contribute to catalysis by horse liver alcohol dehydrogenase. Rubach JK, Plapp BV. Biochemistry 42, 2907-15, (2003). View articlePMID: 12627956

3.Crystal structure of Escherichia coli QOR quinone oxidoreductase complexed with NADPH. Thorn JM, Barton JD, Dixon NE, Ollis DL, Edwards KJ. J. Mol. Biol. 249, 785-99, (1995). View articlePMID: 7602590

4.Characteristics of alcohol/polyol dehydrogenases. The zinc-containing long-chain alcohol dehydrogenases. Jornvall H, Persson B, Jeffery J. Eur. J. Biochem. 167, 195-201, (1987). View articlePMID: 3622514

5.Progressive sequence alignment and molecular evolution of the Zn-containing alcohol dehydrogenase family. Sun HW, Plapp BV. J. Mol. Evol. 34, 522-35, (1992). View articlePMID: 1593644

6.Dual relationships of xylitol and alcohol dehydrogenases in families of two protein types. Persson B, Hallborn J, Walfridsson M, Hahn-Hagerdal B, Keranen S, Penttila M, Jornvall H. FEBS Lett. 324, 9-14, (1993). View articlePMID: 8504864

7.Zeta-crystallin versus other members of the alcohol dehydrogenase super-family. Variability as a functional characteristic. Jornvall H, Persson B, Du Bois GC, Lavers GC, Chen JH, Gonzalez P, Rao PV, Zigler JS Jr. FEBS Lett. 322, 240-4, (1993). View articlePMID: 8486156

Cross References

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.