cd08300

class III alcohol dehydrogenases

CDD entry
Member databaseCDD
CDD typedomain
Short namealcohol_DH_class_III
SetMDR

Description

Members identified as glutathione-dependent formaldehyde dehydrogenase(FDH), a member of the zinc dependent/medium chain alcohol dehydrogenase family. FDH converts formaldehyde and NAD(P) to formate and NAD(P)H. The initial step in this process the spontaneous formation of a S-(hydroxymethyl)glutathione adduct from formaldehyde and glutathione, followed by FDH-mediated oxidation (and detoxification) of the adduct to S-formylglutathione. MDH family uses NAD(H) as a cofactor in the interconversion of alcohols and aldehydes or ketones. Like many zinc-dependent alcohol dehydrogenases (ADH) of the medium chain alcohol dehydrogenase/reductase family (MDR), these FDHs form dimers, with 4 zinc ions per dimer. The medium chain alcohol dehydrogenase family (MDR) have a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. The N-terminal region typically has an all-beta catalytic domain. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit. Alcohol dehydrogenase in the liver converts ethanol and NAD+ to acetaldehyde and NADH, while in yeast and some other microorganisms ADH catalyzes the conversion acetaldehyde to ethanol in alcoholic fermentation. ADH is a member of the medium chain alcohol dehydrogenase family (MDR), which have a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. The NAD(H)-binding region is comprised of 2 structurally similar halves, each of which contacts a mononucleotide. A GxGxxG motif after the first mononucleotide contact half allows the close contact of the coenzyme with the ADH backbone. The N-terminal catalytic domain has a distant homology to GroES. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit, a catalytic zinc at the active site and a structural zinc in a lobe of the catalytic domain. NAD(H) binding occurs in the cleft between the catalytic and coenzyme-binding domains at the active site, and coenzyme binding induces a conformational closing of this cleft. Coenzyme binding typically precedes and contributes to substrate binding.
[1, 11, 4, 7, 3, 6, 8, 2, 9, 5, 10]

References

1.Three-dimensional structure of horse liver alcohol dehydrogenase at 2-4 A resolution. Eklund H, Nordstrom B, Zeppezauer E, Soderlund G, Ohlsson I, Boiwe T, Soderberg BO, Tapia O, Branden CI, Akeson A. J. Mol. Biol. 102, 27-59, (1976). View articlePMID: 178875

2.Medium- and short-chain dehydrogenase/reductase gene and protein families : the MDR superfamily. Persson B, Hedlund J, Jornvall H. Cell. Mol. Life Sci. 65, 3879-94, (2008). View articlePMID: 19011751

3.Comparison of super-secondary structures in proteins. Rao ST, Rossmann MG. J. Mol. Biol. 76, 241-56, (1973). View articlePMID: 4737475

4.Human glutathione-dependent formaldehyde dehydrogenase. Structural changes associated with ternary complex formation. Sanghani PC, Bosron WF, Hurley TD. Biochemistry 41, 15189-94, (2002). View articlePMID: 12484756

5.A super-family of medium-chain dehydrogenases/reductases (MDR). Sub-lines including zeta-crystallin, alcohol and polyol dehydrogenases, quinone oxidoreductase enoyl reductases, VAT-1 and other proteins. Persson B, Zigler JS Jr, Jornvall H. Eur J Biochem 226, 15-22, (1994). PMID: 7957243

6.Medium- and short-chain dehydrogenase/reductase gene and protein families : The role of zinc for alcohol dehydrogenase structure and function. Auld DS, Bergman T. Cell Mol Life Sci 65, 3961-70, (2008). PMID: 19011745

7.NAD-binding domains of dehydrogenases. Lesk AM. Curr. Opin. Struct. Biol. 5, 775-83, (1995). View articlePMID: 8749365

8.Crystallographic investigations of alcohol dehydrogenases. Eklund H, Ramaswamy S, Plapp BV, el-Ahmad M, Danielsson O, Hoog JO, Jornvall H. EXS 71, 269-77, (1994). PMID: 8032158

9.Medium-chain dehydrogenases/reductases (MDR). Family characterizations including genome comparisons and active site modeling. Nordling E, Jornvall H, Persson B. Eur. J. Biochem. 269, 4267-76, (2002). View articlePMID: 12199705

10.Merging protein, gene and genomic data: the evolution of the MDR-ADH family. Gonzalez-Duarte R, Albalat R. Heredity (Edinb) 95, 184-97, (2005). PMID: 16121213

11.Crystal structures of mouse class II alcohol dehydrogenase reveal determinants of substrate specificity and catalytic efficiency. Svensson S, Hoog JO, Schneider G, Sandalova T. J. Mol. Biol. 302, 441-53, (2000). View articlePMID: 10970744

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