Summary: Iron-containing alcohol dehydrogenase
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Alcohol dehydrogenase Edit Wikipedia article
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
Alcohol dehydrogenases (ADH) (EC 18.104.22.168) 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+.
- 1 Evolution
- 2 Discovery
- 3 Properties
- 4 Oxidation of alcohol
- 5 Active site
- 6 Structural zinc site
- 7 Types
- 8 Applications
- 9 Clinical significance
- 10 See also
- 11 References
- 12 External links
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. 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. 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.
The first-ever isolated alcohol dehydrogenase (ADH) was purified in 1937 from Saccharomyces cerevisiae (baker's yeast). Many aspects of the catalytic mechanism for the horse liver ADH enzyme were investigated by Hugo Theorell and coworkers. ADH was also one of the first oligomeric enzymes that had its amino acid sequence and three-dimensional structure determined.
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. In mammals this is a redox (reduction/oxidation) reaction involving the coenzyme nicotinamide adenine dinucleotide (NAD+).
Oxidation of alcohol
Mechanism of action in humans
- Binding of the coenzyme NAD+
- Binding of the alcohol substrate by coordination to zinc
- Deprotonation of His-51
- Deprotonation of nicotinamide ribose
- Deprotonation of Thr-48
- Deprotonation of the alcohol
- Hydride transfer from the alkoxide ion to NAD+, leading to NADH and a zinc bound aldehyde or ketone
- Release of the product aldehyde.
The mechanism in yeast and bacteria is the reverse of this reaction. These steps are supported through kinetic studies.
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. 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.
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+.
Structural zinc site
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.
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. The enzyme is present at high levels in the liver and the lining of the stomach. It catalyzes the oxidation of ethanol to acetaldehyde:
- CH3CH2OH + NAD+ → CH3CHO + NADH + H+
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.
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. The level of activity may not be dependent only on level of expression but also on allelic diversity among the population.
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
In yeast 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.
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. 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. 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. Differences in the sequences of ADH in different species have been used to create phylogenies showing how closely related different species of plants are. 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.
|Iron-containing alcohol dehydrogenase|
bacillus stearothermophilus glycerol dehydrogenase complex with glycerol
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. Members of the iron-containing alcohol dehydrogenase family include:
- Escherichia coli propanediol oxidoreductase EC 22.214.171.124 (gene fucO), an enzyme involved in the metabolism of fucose and which also seems to contain ferrous ion(s).
- Clostridium acetobutylicum NADPH- and NADH-dependent butanol dehydrogenases EC 1.1.1.- (genes adh1, bdhA and bdhB), enzymes that have activity using butanol and ethanol as substrates.
- E. coli adhE, an iron-dependent enzyme that harbours three different activities: alcohol dehydrogenase, acetaldehyde dehydrogenase (acetylating) EC 126.96.36.199 and pyruvate-formate-lyase deactivase.
- Citrobacter freundii and Klebsiella pneumoniae 1,3-propanediol dehydrogenase EC 188.8.131.52 (gene dhaT)
- E. coli hypothetical protein yiaY.
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.
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.
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.
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.
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.
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- 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.
- 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.
- 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.
- 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.
- Negelein E, Wulff HJ (1937). Biochem. Z. 293: 351.
- Theorell H, McKee JS (October 1961). "Mechanism of action of liver alcohol dehydrogenase". Nature 192 (4797): 47–50. doi:10.1038/192047a0. PMID 13920552.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Kovacs B, Stöppler MC. "Alcohol and Nutrition". MedicineNet, Inc. Archived from the original on 23 June 2011. Retrieved 2011-06-07.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Leuchs S, Greiner L (2011). "Alcohol dehydrogenase from Lactobacillus brevis: A versatile catalyst for enenatioselective reduction". CABEQ: 267–281.
- 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.
- 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.
- 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
|Wikimedia Commons has media related to Alcohol dehydrogenase.|
- 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.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Iron-containing alcohol dehydrogenase Provide feedback
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Internal database links
|Similarity to PfamA using HHSearch:||DHQ_synthase Fe-ADH_2|
External database links
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:
- Escherichia coli propanediol oxidoreductase (EC) (gene fucO) [PUBMED:2661535], an enzyme involved in the metabolism of fucose and which also seems to contain ferrous ion(s).
- Clostridium acetobutylicum NADPH- and NADH-dependent butanol dehydrogenases (EC) (genes adh1, bdhA and bdhB) [PUBMED:1385386], an enzyme which has activity using butanol and ethanol as substrates.
- E. coli adhE [PUBMED:2015910], an iron-dependent enzyme which harbor three different activities: alcohol dehydrogenase, acetaldehyde dehydrogenase (acetylating) (EC) and pyruvate-formate-lyase deactivase.
- Bacterial glycerol dehydrogenase (EC) (gene gldA or dhaD) [PUBMED:8132480].
- Clostridium kluyveri NAD-dependent 4-hydroxybutyrate dehydrogenase (4hbd) (EC).
- Citrobacter freundii and Klebsiella pneumoniae 1,3-propanediol dehydrogenase (EC) (gene dhaT).
- Bacillus methanolicus NAD-dependent methanol dehydrogenase (EC) [PUBMED:1644761].
- E. coli and Salmonella typhimurium ethanolamine utilization protein eutG.
- E. coli hypothetical protein yiaY.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||metal ion binding (GO:0046872)|
|oxidoreductase activity (GO:0016491)|
|Biological process||oxidation-reduction process (GO:0055114)|
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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 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...
If you find these logos useful in your own work, please consider citing the following article:
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.
|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 build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||14|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
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.
There are 2 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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.
Loading structure mapping...