DB code: D00021

RLCP classification 4.501.3813400.59 : Addition
9.1050.584160.160 : Hydride transfer
1.14.200.137 : Hydrolysis
CATH domain 3.40.605.10 : Aldehyde Dehydrogenase; Chain A, domain 1 Catalytic domain
3.40.309.10 : Aldehyde Dehydrogenase; Chain A, domain 2 Catalytic domain
E.C. 1.2.1.8 1.2.1.3
CSA 1a4s
M-CSA 1a4s
MACiE M0100

CATH domain Related DB codes (homologues)
3.40.309.10 : Aldehyde Dehydrogenase; Chain A, domain 2 D00020 D00022 D00475 D00614
3.40.605.10 : Aldehyde Dehydrogenase; Chain A, domain 1 D00020 D00022 D00475 D00614

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
P56533 Betaine aldehyde dehydrogenase
BADH
EC 1.2.1.8
Aldehyde dehydrogenase family 9 member A1
EC 1.2.1.3
PF00171 (Aldedh)
[Graphical View]

KEGG enzyme name
betaine-aldehyde dehydrogenase
(EC 1.2.1.8 )
betaine aldehyde oxidase
(EC 1.2.1.8 )
BADH
(EC 1.2.1.8 )
betaine aldehyde dehydrogenase
(EC 1.2.1.8 )
BetB
(EC 1.2.1.8 )
aldehyde dehydrogenase (NAD+)
(EC 1.2.1.3 )
CoA-independent aldehyde dehydrogenase
(EC 1.2.1.3 )
m-methylbenzaldehyde dehydrogenase
(EC 1.2.1.3 )
NAD-aldehyde dehydrogenase
(EC 1.2.1.3 )
NAD-dependent 4-hydroxynonenal dehydrogenase
(EC 1.2.1.3 )
NAD-dependent aldehyde dehydrogenase
(EC 1.2.1.3 )
NAD-linked aldehyde dehydrogenase
(EC 1.2.1.3 )
propionaldehyde dehydrogenase
(EC 1.2.1.3 )
aldehyde dehydrogenase (NAD)
(EC 1.2.1.3 )

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P56533 BADH_GADCA Betaine aldehyde + NAD(+) + H(2)O = betaine + NADH. An aldehyde + NAD(+) + H(2)O = an acid + NADH. Homotetramer. Cytoplasm (By similarity).

KEGG Pathways
Map code Pathways E.C.
MAP00010 Glycolysis / Gluconeogenesis 1.2.1.3
MAP00053 Ascorbate and aldarate metabolism 1.2.1.3
MAP00071 Fatty acid metabolism 1.2.1.3
MAP00120 Bile acid biosynthesis 1.2.1.3
MAP00220 Urea cycle and metabolism of amino groups 1.2.1.3
MAP00260 Glycine, serine and threonine metabolism 1.2.1.8
MAP00280 Valine, leucine and isoleucine degradation 1.2.1.3
MAP00310 Lysine degradation 1.2.1.3
MAP00340 Histidine metabolism 1.2.1.3
MAP00380 Tryptophan metabolism 1.2.1.3
MAP00410 beta-Alanine metabolism 1.2.1.3
MAP00561 Glycerolipid metabolism 1.2.1.3
MAP00620 Pyruvate metabolism 1.2.1.3
MAP00631 1,2-Dichloroethane degradation 1.2.1.3
MAP00640 Propanoate metabolism 1.2.1.3
MAP00641 3-Chloroacrylic acid degradation 1.2.1.3
MAP00650 Butanoate metabolism 1.2.1.3
MAP00903 Limonene and pinene degradation 1.2.1.3

Compound table
Substrates Products Intermediates
KEGG-id C00576 C00071 C00003 C00001 C00719 C00174 C00004 C00080 I00156 I00154 I00155
E.C. 1.2.1.8
1.2.1.3
1.2.1.8
1.2.1.3
1.2.1.8
1.2.1.3
1.2.1.8
1.2.1.3
1.2.1.8
1.2.1.3
1.2.1.8
1.2.1.3
1.2.1.8
1.2.1.3
1.2.1.8
1.2.1.3
1.2.1.8
1.2.1.3
Compound Betaine aldehyde Aldehyde NAD+ H2O Betaine Acid NADH H+ Peptidyl-Cys-alcohol-intermediate Acyl-enzyme(Peptidyl-Cys-acyl group) Peptidyl-Cys-tetrahedral-intermediate
Type amine group,carbohydrate carbohydrate amide group,amine group,nucleotide H2O amine group,carboxyl group carboxyl group amide group,amine group,nucleotide others
ChEBI 15710
15846
15377
17750
16908
15378
PubChem 249
5893
22247451
962
247
439153
1038
1a4sA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1a4sB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1a4sC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1a4sD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bpwA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAD Unbound Unbound Unbound Unbound Unbound Unbound
1bpwB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAD Unbound Unbound Unbound Unbound Unbound Unbound
1bpwC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAD Unbound Unbound Unbound Unbound Unbound Unbound
1bpwD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAD Unbound Unbound Unbound Unbound Unbound Unbound
1a4sA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1a4sB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1a4sC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1a4sD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bpwA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bpwB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bpwC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bpwD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [5]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1a4sA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 166;GLU 263
1a4sB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 166;GLU 263
1a4sC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 166;GLU 263
1a4sD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 166;GLU 263
1bpwA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 166;GLU 263
1bpwB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 166;GLU 263
1bpwC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 166;GLU 263
1bpwD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 166;GLU 263
1a4sA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 297 CYS 297
1a4sB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 297 CYS 297
1a4sC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 297 CYS 297
1a4sD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 297 CYS 297
1bpwA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 297 CYS 297
1bpwB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 297 CYS 297
1bpwC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 297 CYS 297
1bpwD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 297 CYS 297

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
p.239-242
[3]
p.706-709
[5]
p.2114-2115
[6]
p.1546-1549

References
[1]
Resource
Comments
Medline ID
PubMed ID 8269919
Journal Eur J Biochem
Year 1993
Volume 218
Pages 311-20
Authors Kurys G, Shah PC, Kikonygo A, Reed D, Ambroziak W, Pietruszko R
Title Human aldehyde dehydrogenase. cDNA cloning and primary structure of the enzyme that catalyzes dehydrogenation of 4-aminobutyraldehyde.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7819202
Journal Biochemistry
Year 1995
Volume 34
Pages 237-43
Authors Wang X, Weiner H
Title Involvement of glutamate 268 in the active site of human liver mitochondrial (class 2) aldehyde dehydrogenase as probed by site-directed mutagenesis.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9195888
Journal Structure
Year 1997
Volume 5
Pages 701-11
Authors Steinmetz CG, Xie P, Weiner H, Hurley TD
Title Structure of mitochondrial aldehyde dehydrogenase: the genetic component of ethanol aversion.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9228057
Journal J Biol Chem
Year 1997
Volume 272
Pages 18823-6
Authors Ni L, Sheikh S, Weiner H
Title Involvement of glutamate 399 and lysine 192 in the mechanism of human liver mitochondrial aldehyde dehydrogenase.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS)
Medline ID 99006561
PubMed ID 9792097
Journal Protein Sci
Year 1998
Volume 7
Pages 2106-17
Authors Johansson K, El-Ahmad M, Ramaswamy S, Hjelmqvist L, Jornvall H, Eklund H
Title Structure of betaine aldehyde dehydrogenase at 2.1 A resolution.
Related PDB 1a4s 1bpw
Related UniProtKB P56533
[6]
Resource
Comments
Medline ID
PubMed ID 9862807
Journal Structure
Year 1998
Volume 6
Pages 1541-51
Authors Moore SA, Baker HM, Blythe TJ, Kitson KE, Kitson TM, Baker EN
Title Sheep liver cytosolic aldehyde dehydrogenase: the structure reveals the basis for the retinal specificity of class 1 aldehyde dehydrogenases.
Related PDB 1bxs
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10352667
Journal Adv Exp Med Biol
Year 1999
Volume 463
Pages 39-44
Authors Hjelmqvist L, el-Ahmad M, Johansson K, Norin A, Ramaswamy S, Jornvall H
Title Structure and function of betaine aldehyde dehydrogenase. An enzyme within the multienzyme aldehyde dehydrogenase system.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10631996
Journal Protein Sci
Year 1999
Volume 8
Pages 2784-90
Authors Ni L, Zhou J, Hurley TD, Weiner H
Title Human liver mitochondrial aldehyde dehydrogenase: three-dimensional structure and the restoration of solubility and activity of chimeric forms.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11104673
Journal Biochem J
Year 2000
Volume 352
Pages 675-83
Authors Velasco-Garcia R, Gonzalez-Segura L, Munoz-Clares RA
Title Steady-state kinetic mechanism of the NADP+- and NAD+-dependent reactions catalysed by betaine aldehyde dehydrogenase from Pseudomonas aeruginosa.
Related PDB
Related UniProtKB

Comments
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.
(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.
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.
(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.

Created Updated
2004-03-16 2012-10-24