PROSITE documentation PDOC00068

Aldehyde dehydrogenases (EC 1.2.1.3 and EC 1.2.1.5) are enzymes which oxidize a wide variety of aliphatic and aromatic aldehydes. In mammals at least four different forms of the enzyme are known [1]: class-1 (or Ald C) a tetrameric cytosolic enzyme, class-2 (or Ald M) a tetrameric mitochondrial enzyme, class-3 (or Ald D) a dimeric cytosolic enzyme, and class IV a microsomal enzyme. Aldehyde dehydrogenases have also been sequenced from fungal and bacterial species. A number of enzymes are known to be evolutionary related to aldehyde dehydrogenases; these enzymes are listed below.

Plants and bacterial βine-aldehyde dehydrogenase (EC 1.2.1.8) [2], an enzyme that catalyzes the last step in the biosynthesis of βine.
Plants and bacterial NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.9).
Escherichia coli succinate-semialdehyde dehydrogenase (NADP+) (EC 1.2.1.16) (gene gabD) [3], which reduces succinate semialdehyde into succinate.
Escherichia coli lactaldehyde dehydrogenase (EC 1.2.1.22) (gene ald) [4].
Mammalian succinate semialdehyde dehydrogenase (NAD+) (EC 1.2.1.24).
Escherichia coli phenylacetaldehyde dehydrogenase (EC 1.2.1.39).
Escherichia coli 5-carboxymethyl-2-hydroxymuconate semialdehyde dehydrogenase (gene hpcC).
Pseudomonas putida 2-hydroxymuconic semialdehyde dehydrogenase [5] (genes dmpC and xylG), an enzyme in the meta-cleavage pathway for the degradation of phenols, cresols and catechol.
Bacterial and mammalian methylmalonate-semialdehyde dehydrogenase (MMSDH) (EC 1.2.1.27) [6], an enzyme involved in the distal pathway of valine catabolism.
Yeast delta-1-pyrroline-5-carboxylate dehydrogenase (EC 1.5.1.12) [7] (gene PUT2), which converts proline to glutamate.
Bacterial multifunctional putA protein, which contains a delta-1-pyrroline- 5-carboxylate dehydrogenase domain.
26G, a garden pea protein of unknown function which is induced by dehydration of shoots [8].
Mammalian formyltetrahydrofolate dehydrogenase (EC 1.5.1.6) [9]. This is a cytosolic enzyme responsible for the NADP-dependent decarboxylative reduction of 10-formyltetrahydrofolate into tetrahydrofolate. It is an protein of about 900 amino acids which consist of three domains; the C- terminal domain (480 residues) is structurally and functionally related to aldehyde dehydrogenases.
Yeast hypothetical protein YBR006w.
Yeast hypothetical protein YER073w.
Yeast hypothetical protein YHR039c.
Caenorhabditis elegans hypothetical protein F01F1.6.

A glutamic acid and a cysteine residue have been implicated in the catalytic activity of mammalian aldehyde dehydrogenase. These residues are conserved in all the enzymes of this family. We have derived two patterns for this family, one for each of the active site residues.

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Omega-crystallins are minor structural components of squids and octopi eye lens. They are evolutionary related to aldehyde dehydrogenases but have lost their catalytic activity. These patterns will not detect them.

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1	Authors	Hempel J., Harper K., Lindahl R.
	Title	Inducible (class 3) aldehyde dehydrogenase from rat hepatocellular carcinoma and 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated liver: distant relationship to the class 1 and 2 enzymes from mammalian liver cytosol/mitochondria.
	Source	Biochemistry 28:1160-1167(1989).
	PubMed ID	2713359

2	Authors	Weretilnyk E.A., Hanson A.D.
	Title	Molecular cloning of a plant betaine-aldehyde dehydrogenase, an enzyme implicated in adaptation to salinity and drought.
	Source	Proc. Natl. Acad. Sci. U.S.A. 87:2745-2749(1990).
	PubMed ID	2320587

3	Authors	Niegemann E., Schulz A., Bartsch K.
	Title	Molecular organization of the Escherichia coli gab cluster: nucleotide sequence of the structural genes gabD and gabP and expression of the GABA permease gene.
	Source	Arch. Microbiol. 160:454-460(1993).
	PubMed ID	8297211

4	Authors	Hidalgo E., Chen Y.-M., Lin E.C.C., Aguilar J.
	Title	Molecular cloning and DNA sequencing of the Escherichia coli K-12 ald gene encoding aldehyde dehydrogenase.
	Source	J. Bacteriol. 173:6118-6123(1991).
	PubMed ID	1917845

5	Authors	Nordlund I., Shingler V.
	Title	Nucleotide sequences of the meta-cleavage pathway enzymes 2-hydroxymuconic semialdehyde dehydrogenase and 2-hydroxymuconic semialdehyde hydrolase from Pseudomonas CF600.
	Source	Biochim. Biophys. Acta 1049:227-230(1990).
	PubMed ID	2194577

Aldehyde dehydrogenases active sites

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6	Authors	Steele M.I., Lorenz D., Hatter K., Park A., Sokatch J.R.
	Title	Characterization of the mmsAB operon of Pseudomonas aeruginosa PAO encoding methylmalonate-semialdehyde dehydrogenase and 3-hydroxyisobutyrate dehydrogenase.
	Source	J. Biol. Chem. 267:13585-13592(1992).
	PubMed ID	1339433

7	Authors	Krzywicki K.A., Brandriss M.C.
	Title	Primary structure of the nuclear PUT2 gene involved in the mitochondrial pathway for proline utilization in Saccharomyces cerevisiae.
	Source	Mol. Cell. Biol. 4:2837-2842(1984).
	PubMed ID	6098824

8	Authors	Guerrero F.D., Jones J.T., Mullet J.E.
	Title	Turgor-responsive gene transcription and RNA levels increase rapidly when pea shoots are wilted. Sequence and expression of three inducible genes.
	Source	Plant Mol. Biol. 15:11-26(1990).
	PubMed ID	1715781

9	Authors	Cook R.J., Lloyd R.S., Wagner C.
	Title	Isolation and characterization of cDNA clones for rat liver 10-formyltetrahydrofolate dehydrogenase.
	Source	J. Biol. Chem. 266:4965-4973(1991).
	PubMed ID	1848231