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67  structures 3785  species 2  interactions 13485  sequences 23  architectures

Family: Fe-ADH (PF00465)

Summary: Iron-containing alcohol dehydrogenase

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Alcohol dehydrogenase". More...

Alcohol dehydrogenase Edit Wikipedia article

alcohol dehydrogenase
Protein ADH5 PDB 1m6h.png
Crystallographic structure of the
homodimer of human ADH5.[1]
Identifiers
EC number 1.1.1.1
CAS number 9031-72-5
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

Alcohol dehydrogenases (ADH) (EC 1.1.1.1) are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+ to NADH). In humans and many other animals, they serve to break down alcohols that otherwise are toxic, and they also participate in generation of useful aldehyde, ketone, or alcohol groups during biosynthesis of various metabolites. In yeast, plants, and many bacteria, some alcohol dehydrogenases catalyze the opposite reaction as part of fermentation to ensure a constant supply of NAD+.

Evolution

Genetic evidence from comparisons of multiple organisms showed that a glutathione-dependent formaldehyde dehydrogenase, identical to a class III alcohol dehydrogenase (ADH-3/ADH5), is presumed to be the ancestral enzyme for the entire ADH family.[2][3] Early on in evolution, an effective method for eliminating both endogenous and exogenous formaldehyde was important and this capacity has conserved the ancestral ADH-3 through time. From genetic duplications of ADH-3, followed by series of mutations, the other ADHs evolved.[2][3] The ability to produce ethanol from sugar is believed to have initially evolved in yeast. This feature is not adaptive from an energy point of view but, by making alcohol in such high concentrations so that they would be toxic to other organisms, yeast cells could effectively eliminate their competition. Since rotting fruit can contain more than 4% of ethanol, animals eating the fruit needed a system to metabolize exogenous ethanol. This was thought to explain the conservation of ethanol active ADH in other species than yeast, though ADH-3 is now known to also have a major role in nitric oxide signaling.[4][5]

Discovery

Horse LADH (Liver Alcohol Dehydrogenase)

The first-ever isolated alcohol dehydrogenase (ADH) was purified in 1937 from Saccharomyces cerevisiae (baker's yeast).[6] Many aspects of the catalytic mechanism for the horse liver ADH enzyme were investigated by Hugo Theorell and coworkers.[7] ADH was also one of the first oligomeric enzymes that had its amino acid sequence and three-dimensional structure determined.[8][9][10]

In early 1960, it was discovered in fruit flies of the genus Drosophila.[11]

Properties

The alcohol dehydrogenases comprise a group of several isozymes that catalyse the oxidation of primary and secondary alcohols to aldehydes and ketones, respectively, and also can catalyse the reverse reaction.[11] In mammals this is a redox (reduction/oxidation) reaction involving the coenzyme nicotinamide adenine dinucleotide (NAD+).

Alcohol dehydrogenase is a dimer with a mass of 80 kDa.[12]

Oxidation of alcohol

Mechanism of action in humans

Steps

  1. Binding of the coenzyme NAD+
  2. Binding of the alcohol substrate by coordination to zinc
  3. Deprotonation of His-51
  4. Deprotonation of nicotinamide ribose
  5. Deprotonation of Thr-48
  6. Deprotonation of the alcohol
  7. Hydride transfer from the alkoxide ion to NAD+, leading to NADH and a zinc bound aldehyde or ketone
  8. Release of the product aldehyde.

The mechanism in yeast and bacteria is the reverse of this reaction. These steps are supported through kinetic studies.[12]

Involved subunits

The substrate is coordinated to the zinc and this enzyme has two zinc atoms per subunit. One is the active site, which is involved in catalysis. In the active site, the ligands are Cys-46, Cys-174, His-67, and one water molecule. The other subunit is involved with structure. In this mechanism, the hydride from the alcohol goes to NAD+. Crystal structures indicate that the His-51 deprotonates the nicotinamide ribose, which deprotonates Ser-48. Finally, Ser-48 deprotonates the alcohol, making it an aldehyde.[12] From a mechanistic perspective, if the enzyme adds hydride to the re face of NAD+, the resulting hydrogen is incorporated into the pro-R position. Enzymes that add hydride to the re face are deemed Class A dehydrogenases.

Active site

The active site of alcohol dehydrogenase

The active site of human ADH1 (PDB:1HSO) consists of a zinc atom, His-67, Cys-174, Cys-46, Thr-48, His-51, Ile-269, Val-292, Ala-317, and Leu-319. In the commonly studied horse liver isoform, Thr-48 is a Ser, and Leu-319 is a Phe. The zinc coordinates the substrate(alcohol). The zinc is coordinated by Cys-46, Cys-174, and His-67. Leu-319, Ala-317, His-51, Ile-269 and Val-292 stabilize NAD+ by forming hydrogen bonds. His-51 and Ile-269 form hydrogen bonds with the alcohols on nicotinamide ribose. Phe-319, Ala-317 and Val-292 form hydrogen bonds with the amide on NAD+.[12]

Structural zinc site

The structural zinc binding motif in alcohol dehydrogenase from a MD simulation

Mammalian alcohol dehydrogenases also have a structural zinc site. This Zn ion plays a structural role and is crucial for protein stability. The structures of the catalytic and structural zinc sites in horse liver alcohol dehydrogenase (HLADH) as revealed in crystallographic structures, which has been studied computationally with quantum chemical as well as with classical molecular dynamics methods. The structural zinc site is composed of four closely spaced cysteine ligands (Cys97, Cys100, Cys103, and Cys111 in the amino acid sequence) positioned in an almost symmetric tetrahedron around the Zn ion. A recent study showed that the interaction between zinc and cysteine is governed by primarily an electrostatic contribution with an additional covalent contribution to the binding.[13]

Types

Human

In humans, ADH exists in multiple forms as a dimer and is encoded by at least seven different genes. There are five classes (I-V) of alcohol dehydrogenase, but the hepatic form that is used primarily in humans is class 1. Class 1 consists of α, β, and γ subunits that are encoded by the genes ADH1A, ADH1B, and ADH1C.[14] The enzyme is present at high levels in the liver and the lining of the stomach.[15] It catalyzes the oxidation of ethanol to acetaldehyde:

CH3CH2OH + NAD+ → CH3CHO + NADH + H+

This allows the consumption of alcoholic beverages, but its evolutionary purpose is probably the breakdown of alcohols naturally contained in foods or produced by bacteria in the digestive tract.[16]

Another evolutionary purpose may be metabolism of the endogenous alcohol vitamin A (retinol), which generates the hormone retinoic acid, although the function here may be primarily the elimination of toxic levels of retinol.[17][18]

alcohol dehydrogenase 1A,
α polypeptide
Identifiers
Symbol ADH1A
Alt. symbols ADH1
Entrez 124
HUGO 249
OMIM 103700
RefSeq NM_000667
UniProt P07327
Other data
Locus Chr. 4 q23
alcohol dehydrogenase 1B,
β polypeptide
Identifiers
Symbol ADH1B
Alt. symbols ADH2
Entrez 125
HUGO 250
OMIM 103720
RefSeq NM_000668
UniProt P00325
Other data
Locus Chr. 4 q23
alcohol dehydrogenase 1C,
γ polypeptide
Identifiers
Symbol ADH1C
Alt. symbols ADH3
Entrez 126
HUGO 251
OMIM 103730
RefSeq NM_000669
UniProt P00326
Other data
Locus Chr. 4 q23

Alcohol dehydrogenase is also involved in the toxicity of other types of alcohol: For instance, it oxidizes methanol to produce formaldehyde and ethylene glycol to ultimately yield glycolic and oxalic acids. Humans have at least six slightly different alcohol dehydrogenases. Each is a dimer (i.e., consists of two polypeptides), with each dimer containing two zinc ions Zn2+. One of those ions is crucial for the operation of the enzyme: It is located at the catalytic site and holds the hydroxyl group of the alcohol in place.

Alcohol dehydrogenase activity varies between men and women, between young and old, and among populations from different areas of the world. For example, young women are unable to process alcohol at the same rate as young men because they do not express the alcohol dehydrogenase as highly, although the inverse is true among the middle-aged.[19] The level of activity may not be dependent only on level of expression but also on allelic diversity among the population.

The human genes that encode class II, III, IV, and V alcohol dehydrogenases are ADH4, ADH5, ADH7, and ADH6, respectively.

alcohol dehydrogenase 4
(class II), π polypeptide
Identifiers
Symbol ADH4
Entrez 127
HUGO 252
OMIM 103740
RefSeq NM_000670
UniProt P08319
Other data
Locus Chr. 4 q22
alcohol dehydrogenase 5
(class III), χ polypeptide
Identifiers
Symbol ADH5
Entrez 128
HUGO 253
OMIM 103710
RefSeq NM_000671
UniProt P11766
Other data
Locus Chr. 4 q23
alcohol dehydrogenase 6
(class V)
Identifiers
Symbol ADH6
Entrez 130
HUGO 255
OMIM 103735
RefSeq NM_000672
UniProt P28332
Other data
Locus Chr. 4 q23
alcohol dehydrogenase 7
(class IV), μ or σ polypeptide
Identifiers
Symbol ADH7
Entrez 131
HUGO 256
OMIM 600086
RefSeq NM_000673
UniProt P40394
Other data
Locus Chr. 4 q23-q24

Yeast and bacteria

Unlike humans, yeast and bacteria (except lactic acid bacteria, and E. coli in certain conditions) do not ferment glucose to lactate. Instead, they ferment it to ethanol and CO
2
. The overall reaction can be seen below:

Glucose + 2 ADP + 2 Pi → 2 ethanol + 2 CO2 + 2 ATP + 2 H2O[20]
Alcohol Dehydrogenase

In yeast[21] and many bacteria, alcohol dehydrogenase plays an important part in fermentation: Pyruvate resulting from glycolysis is converted to acetaldehyde and carbon dioxide, and the acetaldehyde is then reduced to ethanol by an alcohol dehydrogenase called ADH1. The purpose of this latter step is the regeneration of NAD+, so that the energy-generating glycolysis can continue. Humans exploit this process to produce alcoholic beverages, by letting yeast ferment various fruits or grains. It is interesting to note that yeast can produce and consume their own alcohol.

The main alcohol dehydrogenase in yeast is larger than the human one, consisting of four rather than just two subunits. It also contains zinc at its catalytic site. Together with the zinc-containing alcohol dehydrogenases of animals and humans, these enzymes from yeasts and many bacteria form the family of "long-chain"-alcohol dehydrogenases.

Brewer's yeast also has another alcohol dehydrogenase, ADH2, which evolved out of a duplicate version of the chromosome containing the ADH1 gene. ADH2 is used by the yeast to convert ethanol back into acetaldehyde, and it is expressed only when sugar concentration is low. Having these two enzymes allows yeast to produce alcohol when sugar is plentiful (and this alcohol then kills off competing microbes), and then continue with the oxidation of the alcohol once the sugar, and competition, is gone.[22]

Plants

In plants, ADH catalyses the same reaction as in yeast and bacteria to ensure that there is a constant supply of NAD+. Maize has two versions of ADH - ADH1 and ADH2, Arabidopsis thaliana contains only one ADH gene. The structure of Arabidopsis ADH is 47%-conserved, relative to ADH from horse liver. Structurally and functionally important residues, such as the seven residues that provide ligands for the catalytic and noncatalytic zinc atoms, however, are conserved, suggesting that the enzymes have a similar structure.[23] ADH is constitutively expressed at low levels in the roots of young plants grown on agar. If the roots lack oxygen, the expression of ADH increases significantly.[24] Its expression is also increased in response to dehydration, to low temperatures, and to abscisic acid, and it plays an important role in fruit ripening, seedling development, and pollen development.[25] Differences in the sequences of ADH in different species have been used to create phylogenies showing how closely related different species of plants are.[26] It is an ideal gene to use due to its convenient size (2–3 kb in length with a ~1000 nucleotide coding sequence) and low copy number.[25]

Iron-containing

Iron-containing alcohol dehydrogenase
PDB 1jqa EBI.jpg
bacillus stearothermophilus glycerol dehydrogenase complex with glycerol
Identifiers
Symbol Fe-ADH
Pfam PF00465
Pfam clan CL0224
InterPro IPR001670
PROSITE PDOC00059
SCOP 1jqa
SUPERFAMILY 1jqa

A third family of alcohol dehydrogenases, unrelated to the above two, are iron-containing ones. They occur in bacteria and fungi. In comparison to enzymes the above families, these enzymes are oxygen-sensitive.[citation needed] Members of the iron-containing alcohol dehydrogenase family include:

  • E. coli adhE,[31] an iron-dependent enzyme that harbours three different activities: alcohol dehydrogenase, acetaldehyde dehydrogenase (acetylating) EC 1.2.1.10 and pyruvate-formate-lyase deactivase.
  • E. coli hypothetical protein yiaY.

Other types

A further class of alcohol dehydrogenases belongs to quinoenzymes and requires quinoid cofactors (e.g., pyrroloquinoline quinone, PQQ) as enzyme-bound electron acceptors. A typical example for this type of enzyme is methanol dehydrogenase of methylotrophic bacteria.

Applications

In biotransformation, alcohol dehydrogenases are often used for the synthesis of enantiomerically pure stereoisomers of chiral alcohols. Often, high chemo- and enantioselectivity can be achieved. One example is the alcohol dehydrogenase from Lactobacillus brevis (LbADH), which is described to be a versatile biocatalyst.[34]

In fuel cells, alcohol dehydrogenases can be used to catalyze the breakdown of fuel for an ethanol fuel cell. Scientists at Saint Louis University have used carbon-supported alcohol dehydrogenase with poly(methylene green) as an anode, with a nafion membrane, to achieve about 50 μA/cm2.[35]

In 1949, E. Racker defined one unit of alcohol dehydrogenase activity as the amount that causes a change in optical density of 0.001 per minute under the standard conditions of assay.[36]

Clinical significance

Alcoholism

There have been studies showing that ADH may have an influence on the dependence on ethanol metabolism in alcoholics. Researchers have tentatively detected a few genes to be associated with alcoholism. If the variants of these genes encode slower metabolizing forms of ADH2 and ADH3, there is increased risk of alcoholism. The studies have found that mutations of ADH2 and ADH3 are related to alcoholism in Northeast Asian populations. However, research continues in order to identify the genes and their influence on alcoholism.[37]

Drug dependence

Drug dependence is another problem associated with ADH, which researchers think might be linked to alcoholism. One particular study suggests that drug dependence has seven ADH genes associated with it. These results may lead to treatments that target these specific genes. However, more research is necessary.[38]

See also

References

This article incorporates text from the public domain Pfam and InterPro IPR001670

  1. ^ PDB 1m6h; Sanghani PC, Robinson H, Bosron WF, Hurley TD (September 2002). "Human glutathione-dependent formaldehyde dehydrogenase. Structures of apo, binary, and inhibitory ternary complexes". Biochemistry 41 (35): 10778–86. doi:10.1021/bi0257639. PMID 12196016. 
  2. ^ a b Danielsson O, Jörnvall H (October 1992). ""Enzymogenesis": classical liver alcohol dehydrogenase origin from the glutathione-dependent formaldehyde dehydrogenase line". Proceedings of the National Academy of Sciences of the United States of America 89 (19): 9247–51. doi:10.1073/pnas.89.19.9247. PMC 50103. PMID 1409630. 
  3. ^ a b Persson B, Hedlund J, Jörnvall H (December 2008). "Medium- and short-chain dehydrogenase/reductase gene and protein families : the MDR superfamily". Cell. Mol. Life Sci. 65 (24): 3879–94. doi:10.1007/s00018-008-8587-z. PMC 2792335. PMID 19011751. 
  4. ^ Staab CA, Hellgren M, Höög JO (December 2008). "Medium- and short-chain dehydrogenase/reductase gene and protein families : Dual functions of alcohol dehydrogenase 3: implications with focus on formaldehyde dehydrogenase and S-nitrosoglutathione reductase activities". Cell. Mol. Life Sci. 65 (24): 3950–60. doi:10.1007/s00018-008-8592-2. PMID 19011746. 
  5. ^ Godoy L, Gonzàlez-Duarte R, Albalat R (2006). "S-Nitrosogluthathione reductase activity of amphioxus ADH-3: insights into the nitric oxide metabolism". Int. J. Biol. Sci. 2 (3): 117–24. doi:10.7150/ijbs.2.117. PMC 1458435. PMID 16763671. 
  6. ^ Negelein E, Wulff HJ (1937). Biochem. Z. 293: 351. 
  7. ^ Theorell H, McKee JS (October 1961). "Mechanism of action of liver alcohol dehydrogenase". Nature 192 (4797): 47–50. doi:10.1038/192047a0. PMID 13920552. 
  8. ^ Jörnvall H, Harris JI (April 1970). "Horse liver alcohol dehydrogenase. On the primary structure of the ethanol-active isoenzyme". Eur. J. Biochem. 13 (3): 565–76. doi:10.1111/j.1432-1033.1970.tb00962.x. PMID 5462776. 
  9. ^ Brändén CI, Eklund H, Nordström B, Boiwe T, Söderlund G, Zeppezauer E, Ohlsson I, Akeson A (August 1973). "Structure of liver alcohol dehydrogenase at 2.9-angstrom resolution". Proceedings of the National Academy of Sciences of the United States of America 70 (8): 2439–42. doi:10.1073/pnas.70.8.2439. PMC 433752. PMID 4365379. 
  10. ^ Hellgren M (2009). Enzymatic studies of alcohol dehydrogenase by a combination of in vitro and in silico methods, Ph.D. thesis. Stockholm, Sweden: Karolinska Institutet. p. 70. ISBN 978-91-7409-567-8. 
  11. ^ a b Sofer W, Martin PF (1987). "Analysis of alcohol dehydrogenase gene expression in Drosophila". Annual Review of Genetics 21: 203–25. doi:10.1146/annurev.ge.21.120187.001223. PMID 3327463. 
  12. ^ a b c d Hammes-Schiffer S, Benkovic SJ (2006). "Relating protein motion to catalysis". Annual Review of Biochemistry 75: 519–41. doi:10.1146/annurev.biochem.75.103004.142800. PMID 16756501. 
  13. ^ Erik G. Brandt, Mikko Hellgren, Tore Brinck, Tomas Bergman and Olle Edholm (2009). "Molecular dynamics study of zinc binding to cysteines in a peptide mimic of the alcohol dehydrogenase structural zinc site". Phys. Chem. Chem. Phys. (PCCP) 11 (6): 975–83. doi:10.1039/b815482a. PMID 19177216. 
  14. ^ Sultatos LG, Pastino GM, Rosenfeld CA, Flynn EJ (March 2004). "Incorporation of the genetic control of alcohol dehydrogenase into a physiologically based pharmacokinetic model for ethanol in humans". Toxicological Sciences : an Official Journal of the Society of Toxicology 78 (1): 20–31. doi:10.1093/toxsci/kfh057. PMID 14718645. 
  15. ^ Farrés, james; Moreno, Alberto; Crosas, Bernat; Peralba, Josep M; Allali-Hassani, Abdellah; Hjelmqvist, Lars; Jörnvall, Hans; Parés, Xavier (1994). "Alcohol Dehydrogenase of Class IV (σσ-ADH) from Human Stomach cDNA Sequence and Structure/Function Relationships". European Journal of Biochemistry 224 (2): 549–557. doi:10.1111/j.1432-1033.1994.00549.x. PMID 7925371. 
  16. ^ Kovacs B, Stöppler MC. "Alcohol and Nutrition". MedicineNet, Inc. Archived from the original on 23 June 2011. Retrieved 2011-06-07. 
  17. ^ Duester G (September 2008). "Retinoic acid synthesis and signaling during early organogenesis". Cell 134 (6): 921–31. doi:10.1016/j.cell.2008.09.002. PMC 2632951. PMID 18805086. 
  18. ^ Hellgren, M; Strömberg, P; Gallego, O; Martras, S; Farrés, J; Persson, B; Parés, X; Höög, JO (February 2007). "Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism.". Cellular and molecular life sciences : CMLS 64 (4): 498–505. doi:10.1007/s00018-007-6449-8. PMID 17279314. 
  19. ^ Parlesak A, Billinger MH, Bode C, Bode JC (2002). "Gastric alcohol dehydrogenase activity in man: influence of gender, age, alcohol consumption and smoking in a caucasian population". Alcohol and Alcoholism (Oxford, Oxfordshire) 37 (4): 388–93. doi:10.1093/alcalc/37.4.388. PMID 12107043. 
  20. ^ Cox, Michael; Nelson, David R.; Lehninger, Albert L (2005). Lehninger Principles of Biochemistry. San Francisco: W. H. Freeman. p. 180. ISBN 0-7167-4339-6. 
  21. ^ Leskovac, V.; Trivic, S.; Peričin, D. (December 2002). "The three zinc-containing alcohol dehydrogenases from baker's yeast, Saccharomyces cerevisiae". FEMS Yeast Research 2 (4): 481–494. doi:10.1111/j.1567-1364.2002.tb00116.x. PMID 12702265. 
  22. ^ Coghlan A (23 December 2006). "Festive special: The brewer's tale - life". New Scientist. Archived from the original on 17 March 2009. Retrieved 2009-04-27. 
  23. ^ C Chang and E M Meyerowitz (1 March 1986). "Molecular cloning and DNA sequence of the Arabidopsis thaliana alcohol dehydrogenase gene". Proceedings of the National Academy of Sciences of the United States of America 83 (5): 1408–12. doi:10.1073/pnas.83.5.1408. PMC 323085. PMID 2937058. 
  24. ^ Chung, Hwa-Jee; Robert J. Ferl (October 1999). "Arabidopsis Alcohol Dehydrogenase Expression in Both Shoots and Roots Is Conditioned by Root Growth Environment". Plant Physiology 121 (2): 429–436. doi:10.1104/pp.121.2.429. PMC 59405. PMID 10517834. 
  25. ^ a b Thompson, C.; Fernandes, C.; De Souza, O.; De Freitas, L.; Salzano, F. (2010). "Evaluation of the impact of functional diversification on Poaceae, Brassicaceae, Fabaceae, and Pinaceae alcohol dehydrogenase enzymes". Journal of molecular modeling 16 (5): 919–928. doi:10.1007/s00894-009-0576-0. PMID 19834749.  edit
  26. ^ Jarvinen, P.; Palme, A.; Orlando Morales, L.; Lannenpaa, M.; Keinanen, M.; Sopanen, T.; Lascoux, M. "Phylogenetic relationships of Betula species (Betulaceae) based on nuclear ADH and chloroplast matK sequences - Järvinen et al. 91 (11): 1834 - American Journal of Botany". American Journal of Botany (Amjbot.org) 91 (11): 1834. doi:10.3732/ajb.91.11.1834. Archived from the original on 26 May 2010. Retrieved 2010-07-04. 
  27. ^ Williamson VM, Paquin CE (September 1987). "Homology of Saccharomyces cerevisiae ADH4 to an iron-activated alcohol dehydrogenase from Zymomonas mobilis". Mol. Gen. Genet. 209 (2): 374–81. doi:10.1007/bf00329668. PMID 2823079. 
  28. ^ Conway T, Sewell GW, Osman YA, Ingram LO (June 1987). "Cloning and sequencing of the alcohol dehydrogenase II gene from Zymomonas mobilis". J. Bacteriol. 169 (6): 2591–7. PMC 212129. PMID 3584063. 
  29. ^ Conway T, Ingram LO (July 1989). "Similarity of Escherichia coli propanediol oxidoreductase (fucO product) and an unusual alcohol dehydrogenase from Zymomonas mobilis and Saccharomyces cerevisiae". J. Bacteriol. 171 (7): 3754–9. PMC 210121. PMID 2661535. 
  30. ^ Walter KA, Bennett GN, Papoutsakis ET (November 1992). "Molecular characterization of two Clostridium acetobutylicum ATCC 824 butanol dehydrogenase isozyme genes". J. Bacteriol. 174 (22): 7149–58. PMC 207405. PMID 1385386. 
  31. ^ Kessler D, Leibrecht I, Knappe J (April 1991). "Pyruvate-formate-lyase-deactivase and acetyl-CoA reductase activities of Escherichia coli reside on a polymeric protein particle encoded by adhE". FEBS Lett. 281 (1-2): 59–63. doi:10.1016/0014-5793(91)80358-A. PMID 2015910. 
  32. ^ Truniger V, Boos W (March 1994). "Mapping and cloning of gldA, the structural gene of the Escherichia coli glycerol dehydrogenase". J. Bacteriol. 176 (6): 1796–800. PMC 205274. PMID 8132480. 
  33. ^ de Vries GE, Arfman N, Terpstra P, Dijkhuizen L (August 1992). "Cloning, expression, and sequence analysis of the Bacillus methanolicus C1 methanol dehydrogenase gene". J. Bacteriol. 174 (16): 5346–53. PMC 206372. PMID 1644761. 
  34. ^ Leuchs S, Greiner L (2011). "Alcohol dehydrogenase from Lactobacillus brevis: A versatile catalyst for enenatioselective reduction". CABEQ: 267–281. 
  35. ^ Moore CM, Minteer SD, Martin RS (February 2005). "Microchip-based ethanol/oxygen biofuel cell". Lab on a Chip 5 (2): 218–25. doi:10.1039/b412719f. PMID 15672138. 
  36. ^ http://www.jbc.org/content/184/1/313.full.pdf
  37. ^ Sher KJ, Grekin ER, Williams NA (2005). "The development of alcohol use disorders". Annual Review of Clinical Psychology 1: 493–523. doi:10.1146/annurev.clinpsy.1.102803.144107. PMID 17716097. 
  38. ^ Luo X, Kranzler HR, Zuo L, Wang S, Schork NJ, Gelernter J (February 2007). "Multiple ADH genes modulate risk for drug dependence in both African- and European-Americans". Human Molecular Genetics 16 (4): 380–90. doi:10.1093/hmg/ddl460. PMC 1853246. PMID 17185388. 
  • Taken from California State Polytechnic University, Pomona - pg. 23 in Experiments in General Biochemistry Chemistry 321, 327 by Charles E. Bowen. Revised - November, 2005

External links

  • PDBsum has links to three-dimensional structures of various alcohol dehydrogenases contained in the Protein Data Bank
  • ExPASy contains links to the alcohol dehydrogenase sequences in Swiss-Prot, to a Medline literature search about the enzyme, and to entries in other databases.

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Iron-containing alcohol dehydrogenase Provide feedback

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Internal database links

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This tab holds annotation information from the InterPro database.

InterPro entry IPR001670

Alcohol dehydrogenase (EC) (ADH) catalyzes the reversible oxidation of ethanol to acetaldehyde with the concomitant reduction of NAD. 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.

Iron-containing ADH's have been found in yeast (gene ADH4) [PUBMED:3584063], as well as in Zymomonas mobilis (gene adhB) [PUBMED:2823079]. These two iron-containing ADH's are closely related to the following enzymes:

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan DHQS (CL0224), which has the following description:

This superfamily includes Dehydroquinate synthase and Iron containing alcohol dehydrogenase which have a similar active site organisation [1].

The clan contains the following 3 members:

DHQ_synthase Fe-ADH Fe-ADH_2

Alignments

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Family
Author: Finn RD
Number in seed: 226
Number in full: 13485
Average length of the domain: 355.90 aa
Average identity of full alignment: 25 %
Average coverage of the sequence by the domain: 79.39 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.8 25.8
Trusted cut-off 25.8 25.8
Noise cut-off 25.7 25.7
Model length: 366
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

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Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There are 2 interactions for this family. More...

DHQ_synthase Fe-ADH

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Fe-ADH domain has been found. There are 67 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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