PROSITE documentation PDOC00068

Aldehyde dehydrogenases active sites

Description

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.

Note:

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.

Expert(s) to contact by email:

Joernvall H.
 Persson B.

Last update:

April 2006 / Pattern revised.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

ALDEHYDE_DEHYDR_CYS, PS00070; Aldehyde dehydrogenases cysteine active site  (PATTERN)
Consensus pattern: [FYLVA]-x-{GVEP}-{DILV}-G-[QE]-{LPYG}-C-[LIVMGSTANC]-[AGCN]-{HE}-[GSTADNEKR]
C is the active site residue
Sequences known to belong to this class detected by the pattern: ALL, except for 13 sequences
Other sequence(s) detected in Swiss-Prot: 90.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00070
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00070
• Scan Swiss-Prot/TrEMBL entries against PS00070
• view ligand binding statistics
Matching PDB structures: 1A4S 1A4Z 1AD3 1AG8 ... [ALL]
ALDEHYDE_DEHYDR_GLU, PS00687; Aldehyde dehydrogenases glutamic acid active site  (PATTERN)
Consensus pattern: [LIVMFGA]-E-[LIMSTAC]-[GS]-G-[KNLM]-[SADN]-[TAPFV]
E is the active site residue
Sequences known to belong to this class detected by the pattern: ALL, except for 13 sequences
Other sequence(s) detected in Swiss-Prot: 44.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00687
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00687
• Scan Swiss-Prot/TrEMBL entries against PS00687
• view ligand binding statistics
Matching PDB structures: 1A4S 1A4Z 1AD3 1AG8 ... [ALL]

References

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
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

Copyright

PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)