D00021
type: Enzyme
rlcp: p59
rlcp: p160
rlcp: p137
cath: Aldehyde Dehydrogenase; Chain A, domain 1
cath: Aldehyde Dehydrogenase; Chain A, domain 2
ec: https://purl.uniprot.org/enzyme/1.2.1.8
ec: https://purl.uniprot.org/enzyme/1.2.1.3
csa: 1a4s
macie: M0100
uniprot: P56533
kegg enzyme: betaine-aldehyde dehydrogenase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/1.2.1.8
kegg enzyme: betaine aldehyde oxidase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/1.2.1.8
kegg enzyme: BADH
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/1.2.1.8
kegg enzyme: betaine aldehyde dehydrogenase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/1.2.1.8
kegg enzyme: BetB
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/1.2.1.8
kegg enzyme: aldehyde dehydrogenase (NAD+)
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/1.2.1.3
kegg enzyme: CoA-independent aldehyde dehydrogenase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/1.2.1.3
kegg enzyme: m-methylbenzaldehyde dehydrogenase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/1.2.1.3
kegg enzyme: NAD-aldehyde dehydrogenase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/1.2.1.3
kegg enzyme: NAD-dependent 4-hydroxynonenal dehydrogenase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/1.2.1.3
kegg enzyme: NAD-dependent aldehyde dehydrogenase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/1.2.1.3
kegg enzyme: NAD-linked aldehyde dehydrogenase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/1.2.1.3
kegg enzyme: propionaldehyde dehydrogenase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/1.2.1.3
kegg pathway: Glycolysis / Gluconeogenesis
kegg pathway: Ascorbate and aldarate metabolism
kegg pathway: Fatty acid metabolism
kegg pathway: Bile acid biosynthesis
kegg pathway: Urea cycle and metabolism of amino groups
kegg pathway: Glycine, serine and threonine metabolism
kegg pathway: Valine, leucine and isoleucine degradation
kegg pathway: Lysine degradation
kegg pathway: Histidine metabolism
kegg pathway: Tryptophan metabolism
kegg pathway: beta-Alanine metabolism
kegg pathway: Glycerolipid metabolism
kegg pathway: Pyruvate metabolism
kegg pathway: 1,2-Dichloroethane degradation
kegg pathway: Propanoate metabolism
kegg pathway: 3-Chloroacrylic acid degradation
kegg pathway: Butanoate metabolism
kegg pathway: Limonene and pinene degradation
kegg substrate: Betaine aldehyde
kegg substrate: Aldehyde
kegg substrate: NAD+
kegg substrate: H2O
kegg product: Betaine
kegg product: Acid
kegg product: NADH
kegg product: H+
kegg intermediate: Peptidyl-Cys-alcohol-intermediate
kegg intermediate: Acyl-enzyme(Peptidyl-Cys-acyl group)
kegg intermediate: Peptidyl-Cys-tetrahedral-intermediate
pdb: 1a4sA01
pdb: 1a4sB01
pdb: 1a4sC01
pdb: 1a4sD01
pdb: 1bpwA01
pdb: 1bpwB01
pdb: 1bpwC01
pdb: 1bpwD01
pdb: 1a4sA02
pdb: 1a4sB02
pdb: 1a4sC02
pdb: 1a4sD02
pdb: 1bpwA02
pdb: 1bpwB02
pdb: 1bpwC02
pdb: 1bpwD02
active site residues resources: Sheep liver cytosolic aldehyde dehydrogenase: the structure reveals the basis for the retinal specificity of class 1 aldehyde dehydrogenases.
references: Human aldehyde dehydrogenase. cDNA cloning and primary structure of the enzyme that catalyzes dehydrogenation of 4-aminobutyraldehyde.
references: Involvement of glutamate 268 in the active site of human liver mitochondrial (class 2) aldehyde dehydrogenase as probed by site-directed mutagenesis.
references: Structure of mitochondrial aldehyde dehydrogenase: the genetic component of ethanol aversion.
references: Involvement of glutamate 399 and lysine 192 in the mechanism of human liver mitochondrial aldehyde dehydrogenase.
references: Structure of betaine aldehyde dehydrogenase at 2.1 A resolution.
references: Sheep liver cytosolic aldehyde dehydrogenase: the structure reveals the basis for the retinal specificity of class 1 aldehyde dehydrogenases.
references: Structure and function of betaine aldehyde dehydrogenase. An enzyme within the multienzyme aldehyde dehydrogenase system.
references: Human liver mitochondrial aldehyde dehydrogenase: three-dimensional structure and the restoration of solubility and activity of chimeric forms.
references: Steady-state kinetic mechanism of the NADP+- and NAD+-dependent reactions catalysed by betaine aldehyde dehydrogenase from Pseudomonas aeruginosa.
comment: This enzyme belongs to aldehyde dehydrogenase family. This enzyme is homologous to other aldehyde dehydrogenases (D00020, D00022, D00475 and D00614). This dehydrogenase family shares a nucleophilic cysteine residue at the active site. During the reactions, the conformations of Glu263 and NAD may change, showing two different conformers, a passive mode and active mode (see [6]). According to the literature [2], [3], [5], [6], this enzyme catalyzes the following reactions: (A) Addition of nucleophilic cysteine residue to carbonyl carbon of substrate, forming a thiohemiacetal intermediate (I00156): (A0) Glu263 may act as a general base to activate Cys297. At least, Glu263 may have to deprotonate Cys297 indirectly through a water molecule. (A1) Cys297 makes a nucleophilic attack on the carbonyl carbon of substrate aldehyde, forming a covalent bond with it. This reaction leads to the formation of a thiohemiacetal intermediate (I00156). (A2) The oxyanion of the intermediate can be stabilized by the sidechain of Asn166 and the mainchain amide of Cys297. (B) Hydride transfer from the thiohemiacetal intermediate (I00156) to nicotinamide of NAD, forming a thioacyl intermediate (I00154): (B0) The oxyanion may be stabilized by Asn166 and the mainchain amide of Cys297. (B1) Hydride transfer from carbon atom of the nicotinamide of NAD. This reaction leads to formation of thioacyl intermediate (I00154). (C) Hydrolysis of the thioacyl intermediate (I00154): (C1) Glu263 acts as a general base to activate a water molecule. (C2) The activated water makes a nucleophilic attack on the thioacyl carbon of the intermediate (I00154). This reaction leads to formation of a tetrahedral intermediate (I00155). The oxyanion of the intermediate can be stabilized by the sidechain of Asn166 and the mainchain of Cys297. (C3) Finally, Cys297 is eliminated from the intermediate (I00155). Glu263 may protonate leaving Cys297 through a water.

Aldehyde Dehydrogenase; Chain A, domain 1
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.40.605.10
catalytic domain: index.html

Aldehyde Dehydrogenase; Chain A, domain 2
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.40.309.10
catalytic domain: index.html

Glycolysis / Gluconeogenesis
type: KeggPathway
references: KEGG:MAP00010
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Ascorbate and aldarate metabolism
type: KeggPathway
references: KEGG:MAP00053
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Fatty acid metabolism
type: KeggPathway
references: KEGG:MAP00071
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Bile acid biosynthesis
type: KeggPathway
references: KEGG:MAP00120
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Urea cycle and metabolism of amino groups
type: KeggPathway
references: KEGG:MAP00220
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Glycine, serine and threonine metabolism
type: KeggPathway
references: KEGG:MAP00260
ec: https://purl.uniprot.org/enzyme/1.2.1.8

Valine, leucine and isoleucine degradation
type: KeggPathway
references: KEGG:MAP00280
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Lysine degradation
type: KeggPathway
references: KEGG:MAP00310
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Histidine metabolism
type: KeggPathway
references: KEGG:MAP00340
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Tryptophan metabolism
type: KeggPathway
references: KEGG:MAP00380
ec: https://purl.uniprot.org/enzyme/1.2.1.3

beta-Alanine metabolism
type: KeggPathway
references: KEGG:MAP00410
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Glycerolipid metabolism
type: KeggPathway
references: KEGG:MAP00561
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Pyruvate metabolism
type: KeggPathway
references: KEGG:MAP00620
ec: https://purl.uniprot.org/enzyme/1.2.1.3

1,2-Dichloroethane degradation
type: KeggPathway
references: KEGG:MAP00631
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Propanoate metabolism
type: KeggPathway
references: KEGG:MAP00640
ec: https://purl.uniprot.org/enzyme/1.2.1.3

3-Chloroacrylic acid degradation
type: KeggPathway
references: KEGG:MAP00641
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Butanoate metabolism
type: KeggPathway
references: KEGG:MAP00650
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Limonene and pinene degradation
type: KeggPathway
references: KEGG:MAP00903
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Betaine aldehyde
type: KeggSubstrate
references: KEGG:C00576
ec: https://purl.uniprot.org/enzyme/1.2.1.8
compound type: amine group
compound type: carbohydrate
references: CHEBI:15710
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Aldehyde
type: KeggSubstrate
references: KEGG:C00071
ec: https://purl.uniprot.org/enzyme/1.2.1.3
compound type: carbohydrate

NAD+
type: KeggSubstrate
references: KEGG:C00003
ec: https://purl.uniprot.org/enzyme/1.2.1.8
ec: https://purl.uniprot.org/enzyme/1.2.1.3
compound type: amide group
compound type: amine group
compound type: nucleotide
references: CHEBI:15846
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

H2O
type: KeggSubstrate
references: KEGG:C00001
ec: https://purl.uniprot.org/enzyme/1.2.1.8
ec: https://purl.uniprot.org/enzyme/1.2.1.3
compound type: H2O
references: CHEBI:15377
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Betaine
type: KeggProduct
references: KEGG:C00719
ec: https://purl.uniprot.org/enzyme/1.2.1.8
compound type: amine group
compound type: carboxyl group
references: CHEBI:17750
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Acid
type: KeggProduct
references: KEGG:C00174
ec: https://purl.uniprot.org/enzyme/1.2.1.3
compound type: carboxyl group

NADH
type: KeggProduct
references: KEGG:C00004
ec: https://purl.uniprot.org/enzyme/1.2.1.8
ec: https://purl.uniprot.org/enzyme/1.2.1.3
compound type: amide group
compound type: amine group
compound type: nucleotide
references: CHEBI:16908
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

H+
type: KeggProduct
references: KEGG:C00080
ec: https://purl.uniprot.org/enzyme/1.2.1.8
ec: https://purl.uniprot.org/enzyme/1.2.1.3
compound type: others
references: CHEBI:15378
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Peptidyl-Cys-alcohol-intermediate
type: KeggIntermediate
references: KEGG:I00156
ec: https://purl.uniprot.org/enzyme/1.2.1.8
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Acyl-enzyme(Peptidyl-Cys-acyl group)
type: KeggIntermediate
references: KEGG:I00154
ec: https://purl.uniprot.org/enzyme/1.2.1.8
ec: https://purl.uniprot.org/enzyme/1.2.1.3

Peptidyl-Cys-tetrahedral-intermediate
type: KeggIntermediate
references: KEGG:I00155
ec: https://purl.uniprot.org/enzyme/1.2.1.8
ec: https://purl.uniprot.org/enzyme/1.2.1.3

1a4sA01
type: Pdb
references: 1a4s
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a4s
catalytic residue: ASN 166;GLU 263

1a4sB01
type: Pdb
references: 1a4s
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a4s
catalytic residue: ASN 166;GLU 263

1a4sC01
type: Pdb
references: 1a4s
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a4s
catalytic residue: ASN 166;GLU 263

1a4sD01
type: Pdb
references: 1a4s
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a4s
catalytic residue: ASN 166;GLU 263

1bpwA01
type: Pdb
references: 1bpw
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bpw
catalytic residue: ASN 166;GLU 263

1bpwB01
type: Pdb
references: 1bpw
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bpw
catalytic residue: ASN 166;GLU 263

1bpwC01
type: Pdb
references: 1bpw
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bpw
catalytic residue: ASN 166;GLU 263

1bpwD01
type: Pdb
references: 1bpw
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bpw
catalytic residue: ASN 166;GLU 263

1a4sA02
type: Pdb
references: 1a4s
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a4s
catalytic residue: CYS 297
main chain in catalysis: CYS 297

1a4sB02
type: Pdb
references: 1a4s
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a4s
catalytic residue: CYS 297
main chain in catalysis: CYS 297

1a4sC02
type: Pdb
references: 1a4s
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a4s
catalytic residue: CYS 297
main chain in catalysis: CYS 297

1a4sD02
type: Pdb
references: 1a4s
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a4s
catalytic residue: CYS 297
main chain in catalysis: CYS 297

1bpwA02
type: Pdb
references: 1bpw
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bpw
catalytic residue: CYS 297
main chain in catalysis: CYS 297

1bpwB02
type: Pdb
references: 1bpw
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bpw
catalytic residue: CYS 297
main chain in catalysis: CYS 297

1bpwC02
type: Pdb
references: 1bpw
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bpw
catalytic residue: CYS 297
main chain in catalysis: CYS 297

1bpwD02
type: Pdb
references: 1bpw
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bpw
catalytic residue: CYS 297
main chain in catalysis: CYS 297

Human aldehyde dehydrogenase. cDNA cloning and primary structure of the enzyme that catalyzes dehydrogenation of 4-aminobutyraldehyde.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8269919
journal: Eur J Biochem
volume: 218
pages: 311-20
published year: 1993
authors:
  item: Kurys G
  item: Shah PC
  item: Kikonygo A
  item: Reed D
  item: Ambroziak W
  item: Pietruszko R

Involvement of glutamate 268 in the active site of human liver mitochondrial (class 2) aldehyde dehydrogenase as probed by site-directed mutagenesis.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7819202
journal: Biochemistry
volume: 34
pages: 237-43
published year: 1995
authors:
  item: Wang X
  item: Weiner H

Structure of mitochondrial aldehyde dehydrogenase: the genetic component of ethanol aversion.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9195888
journal: Structure
volume: 5
pages: 701-11
published year: 1997
authors:
  item: Steinmetz CG
  item: Xie P
  item: Weiner H
  item: Hurley TD

Involvement of glutamate 399 and lysine 192 in the mechanism of human liver mitochondrial aldehyde dehydrogenase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9228057
journal: J Biol Chem
volume: 272
pages: 18823-6
published year: 1997
authors:
  item: Ni L
  item: Sheikh S
  item: Weiner H

Structure of betaine aldehyde dehydrogenase at 2.1 A resolution.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS)
medline id: 99006561
references: http://www.ncbi.nlm.nih.gov/pubmed/9792097
journal: Protein Sci
volume: 7
pages: 2106-17
published year: 1998
authors:
  item: Johansson K
  item: El-Ahmad M
  item: Ramaswamy S
  item: Hjelmqvist L
  item: Jornvall H
  item: Eklund H
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P56533

Sheep liver cytosolic aldehyde dehydrogenase: the structure reveals the basis for the retinal specificity of class 1 aldehyde dehydrogenases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9862807
journal: Structure
volume: 6
pages: 1541-51
published year: 1998
authors:
  item: Moore SA
  item: Baker HM
  item: Blythe TJ
  item: Kitson KE
  item: Kitson TM
  item: Baker EN
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Structure and function of betaine aldehyde dehydrogenase. An enzyme within the multienzyme aldehyde dehydrogenase system.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10352667
journal: Adv Exp Med Biol
volume: 463
pages: 39-44
published year: 1999
authors:
  item: Hjelmqvist L
  item: el-Ahmad M
  item: Johansson K
  item: Norin A
  item: Ramaswamy S
  item: Jornvall H

Human liver mitochondrial aldehyde dehydrogenase: three-dimensional structure and the restoration of solubility and activity of chimeric forms.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10631996
journal: Protein Sci
volume: 8
pages: 2784-90
published year: 1999
authors:
  item: Ni L
  item: Zhou J
  item: Hurley TD
  item: Weiner H

Steady-state kinetic mechanism of the NADP+- and NAD+-dependent reactions catalysed by betaine aldehyde dehydrogenase from Pseudomonas aeruginosa.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11104673
journal: Biochem J
volume: 352
pages: 675-83
published year: 2000
authors:
  item: Velasco-Garcia R
  item: Gonzalez-Segura L
  item: Munoz-Clares RA

aldehyde dehydrogenase (NAD)
type: KeggEnzyme
ec: https://purl.uniprot.org/enzyme/1.2.1.3

ReferenceForCatalyticMechanism
reference index: 2
reference section: p.239-242

ReferenceForCatalyticMechanism
reference index: 3
reference section: p.706-709

ReferenceForCatalyticMechanism
reference index: 5
reference section: p.2114-2115

ReferenceForCatalyticMechanism
reference index: 6
reference section: p.1546-1549