EzCatDB: D00021
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DB codeD00021
RLCP classification4.501.3813400.59 : Addition
9.1050.584160.160 : Hydride transfer
1.14.200.137 : Hydrolysis
CATH domainDomain 13.40.605.10 : Aldehyde Dehydrogenase; Chain A, domain 1Catalytic domain
Domain 23.40.309.10 : Aldehyde Dehydrogenase; Chain A, domain 2Catalytic domain
E.C.1.2.1.8,1.2.1.3
CSA1a4s
MACiEM0100

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

Enzyme Name
UniProtKBKEGG

P56533
Protein nameBetaine aldehyde dehydrogenasebetaine-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)

SynonymsBADH
EC 1.2.1.8
Aldehyde dehydrogenase family 9 member A1
EC 1.2.1.3
PfamPF00171 (Aldedh)
[Graphical view]

KEGG pathways
MAP codePathwaysE.C.
MAP00010Glycolysis / Gluconeogenesis1.2.1.3
MAP00053Ascorbate and aldarate metabolism1.2.1.3
MAP00071Fatty acid metabolism1.2.1.3
MAP00120Bile acid biosynthesis1.2.1.3
MAP00220Urea cycle and metabolism of amino groups1.2.1.3
MAP00260Glycine, serine and threonine metabolism1.2.1.8
MAP00280Valine, leucine and isoleucine degradation1.2.1.3
MAP00310Lysine degradation1.2.1.3
MAP00340Histidine metabolism1.2.1.3
MAP00380Tryptophan metabolism1.2.1.3
MAP00410beta-Alanine metabolism1.2.1.3
MAP00561Glycerolipid metabolism1.2.1.3
MAP00620Pyruvate metabolism1.2.1.3
MAP006311,2-Dichloroethane degradation1.2.1.3
MAP00640Propanoate metabolism1.2.1.3
MAP006413-Chloroacrylic acid degradation1.2.1.3
MAP00650Butanoate metabolism1.2.1.3
MAP00903Limonene and pinene degradation1.2.1.3

UniProtKB:Accession NumberP56533
Entry nameBADH_GADCA
ActivityBetaine aldehyde + NAD(+) + H(2)O = betaine + NADH.,An aldehyde + NAD(+) + H(2)O = an acid + NADH.
SubunitHomotetramer.
Subcellular locationCytoplasm (By similarity).
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00576C00071C00003C00001C00719C00174C00004C00080I00156I00154I00155
E.C.1.2.1.81.2.1.31.2.1.8,1.2.1.31.2.1.8,1.2.1.31.2.1.81.2.1.31.2.1.8,1.2.1.31.2.1.8,1.2.1.31.2.1.8,1.2.1.31.2.1.8,1.2.1.31.2.1.8,1.2.1.3
CompoundBetaine aldehydeAldehydeNAD+H2OBetaineAcidNADHH+Peptidyl-Cys-alcohol-intermediateAcyl-enzyme(Peptidyl-Cys-acyl group)Peptidyl-Cys-tetrahedral-intermediate
Typeamine group,carbohydratecarbohydrateamide group,amine group,nucleotideH2Oamine group,carboxyl groupcarboxyl groupamide group,amine group,nucleotideothers


ChEBI15710

15846
15377
17750

16908
15378



PubChem249

5893
962
22247451
247

439153
1038



                   
1a4sA01UnboundUnboundUnbound UnboundUnboundUnbound UnboundUnboundUnbound
1a4sB01UnboundUnboundUnbound UnboundUnboundUnbound UnboundUnboundUnbound
1a4sC01UnboundUnboundUnbound UnboundUnboundUnbound UnboundUnboundUnbound
1a4sD01UnboundUnboundUnbound UnboundUnboundUnbound UnboundUnboundUnbound
1bpwA01UnboundUnboundBound:NAD UnboundUnboundUnbound UnboundUnboundUnbound
1bpwB01UnboundUnboundBound:NAD UnboundUnboundUnbound UnboundUnboundUnbound
1bpwC01UnboundUnboundBound:NAD UnboundUnboundUnbound UnboundUnboundUnbound
1bpwD01UnboundUnboundBound:NAD UnboundUnboundUnbound UnboundUnboundUnbound
1a4sA02UnboundUnboundUnbound UnboundUnboundUnbound UnboundUnboundUnbound
1a4sB02UnboundUnboundUnbound UnboundUnboundUnbound UnboundUnboundUnbound
1a4sC02UnboundUnboundUnbound UnboundUnboundUnbound UnboundUnboundUnbound
1a4sD02UnboundUnboundUnbound UnboundUnboundUnbound UnboundUnboundUnbound
1bpwA02UnboundUnboundUnbound UnboundUnboundUnbound UnboundUnboundUnbound
1bpwB02UnboundUnboundUnbound UnboundUnboundUnbound UnboundUnboundUnbound
1bpwC02UnboundUnboundUnbound UnboundUnboundUnbound UnboundUnboundUnbound
1bpwD02UnboundUnboundUnbound UnboundUnboundUnbound UnboundUnboundUnbound

Active-site residues
resource
literature [5]
pdbCatalytic residuesMain-chain involved in catalysis
          
1a4sA01ASN 166;GLU 263
 
1a4sB01ASN 166;GLU 263
 
1a4sC01ASN 166;GLU 263
 
1a4sD01ASN 166;GLU 263
 
1bpwA01ASN 166;GLU 263
 
1bpwB01ASN 166;GLU 263
 
1bpwC01ASN 166;GLU 263
 
1bpwD01ASN 166;GLU 263
 
1a4sA02CYS 297
CYS 297
1a4sB02CYS 297
CYS 297
1a4sC02CYS 297
CYS 297
1a4sD02CYS 297
CYS 297
1bpwA02CYS 297
CYS 297
1bpwB02CYS 297
CYS 297
1bpwC02CYS 297
CYS 297
1bpwD02CYS 297
CYS 297

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]p.239-242
[3]p.706-709
[5]p.2114-2115
[6]p.1546-1549

references
[1]
PubMed ID8269919
JournalEur J Biochem
Year1993
Volume218
Pages311-20
AuthorsKurys G, Shah PC, Kikonygo A, Reed D, Ambroziak W, Pietruszko R
TitleHuman aldehyde dehydrogenase. cDNA cloning and primary structure of the enzyme that catalyzes dehydrogenation of 4-aminobutyraldehyde.
[2]
PubMed ID7819202
JournalBiochemistry
Year1995
Volume34
Pages237-43
AuthorsWang X, Weiner H
TitleInvolvement of glutamate 268 in the active site of human liver mitochondrial (class 2) aldehyde dehydrogenase as probed by site-directed mutagenesis.
[3]
PubMed ID9195888
JournalStructure
Year1997
Volume5
Pages701-11
AuthorsSteinmetz CG, Xie P, Weiner H, Hurley TD
TitleStructure of mitochondrial aldehyde dehydrogenase: the genetic component of ethanol aversion.
[4]
PubMed ID9228057
JournalJ Biol Chem
Year1997
Volume272
Pages18823-6
AuthorsNi L, Sheikh S, Weiner H
TitleInvolvement of glutamate 399 and lysine 192 in the mechanism of human liver mitochondrial aldehyde dehydrogenase.
[5]
CommentsX-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS)
Medline ID99006561
PubMed ID9792097
JournalProtein Sci
Year1998
Volume7
Pages2106-17
AuthorsJohansson K, El-Ahmad M, Ramaswamy S, Hjelmqvist L, Jornvall H, Eklund H
TitleStructure of betaine aldehyde dehydrogenase at 2.1 A resolution.
Related PDB1a4s,1bpw
Related UniProtKBP56533
[6]
PubMed ID9862807
JournalStructure
Year1998
Volume6
Pages1541-51
AuthorsMoore SA, Baker HM, Blythe TJ, Kitson KE, Kitson TM, Baker EN
TitleSheep liver cytosolic aldehyde dehydrogenase: the structure reveals the basis for the retinal specificity of class 1 aldehyde dehydrogenases.
Related PDB1bxs
[7]
PubMed ID10352667
JournalAdv Exp Med Biol
Year1999
Volume463
Pages39-44
AuthorsHjelmqvist L, el-Ahmad M, Johansson K, Norin A, Ramaswamy S, Jornvall H
TitleStructure and function of betaine aldehyde dehydrogenase. An enzyme within the multienzyme aldehyde dehydrogenase system.
[8]
PubMed ID10631996
JournalProtein Sci
Year1999
Volume8
Pages2784-90
AuthorsNi L, Zhou J, Hurley TD, Weiner H
TitleHuman liver mitochondrial aldehyde dehydrogenase: three-dimensional structure and the restoration of solubility and activity of chimeric forms.
[9]
PubMed ID11104673
JournalBiochem J
Year2000
Volume352
Pages675-83
AuthorsVelasco-Garcia R, Gonzalez-Segura L, Munoz-Clares RA
TitleSteady-state kinetic mechanism of the NADP+- and NAD+-dependent reactions catalysed by betaine aldehyde dehydrogenase from Pseudomonas aeruginosa.

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.
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.

createdupdated
2004-03-162012-10-24


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