EzCatDB: D00615
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DB codeD00615
CATH domainDomain 13.90.180.10 : Quinone Oxidoreductase; Chain A, domain 1Catalytic domain
Domain 23.40.50.720 : Rossmann foldCatalytic domain
E.C.1.2.1.46

CATH domainRelated DB codes (homologues)
3.40.50.720 : Rossmann foldS00543,S00551,S00552,S00553,S00602,S00604,S00605,S00608,S00610,S00625,S00319,S00328,S00329,S00330,S00331,S00332,D00456,D00457,D00458,S00324,S00320,S00325,S00326,S00327,D00459,S00335,S00336,S00334,T00219,S00339,D00513,D00001,D00002,D00003,D00005,D00007,D00008,D00010,D00012,D00017,D00018,D00023,D00027,D00028,D00031,D00032,D00033,D00034,D00035,D00037,D00048,D00071,D00476,D00481,D00482,D00490,D00492,D00494,D00545,D00601,D00603,D00604,D00605,D00845,D00857,D00858,M00161,M00171,M00210,T00002,T00010,T00011,T00015,T00227,T00247,T00408,T00414,D00827,D00262,D00274,D00275,M00035,T00109
3.90.180.10 : Quinone Oxidoreductase; Chain A, domain 1D00001,D00002,D00018,D00048,D00481,D00482,D00490,D00492

Enzyme Name
UniProtKBKEGG

P46154
Protein nameGlutathione-independent formaldehyde dehydrogenaseFormaldehyde dehydrogenase
NAD+-linked formaldehyde dehydrogenase
NAD+-dependent formaldehyde dehydrogenase
SynonymsFALDH
FDH
EC 1.2.1.46
PfamPF08240 (ADH_N)
PF01262 (AlaDh_PNT_C)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00625Chloroalkane and chloroalkene degradation
MAP00680Methane metabolism

UniProtKB:Accession NumberP46154
Entry nameFADH_PSEPU
ActivityFormaldehyde + NAD(+) + H(2)O = formate + NADH.,An alcohol + NAD(+) = an aldehyde or ketone + NADH.
SubunitHomotetramer.
Subcellular location
CofactorBinds 2 zinc ions per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00038C00067C00003C00001C00058C00004C00080I00152
CompoundZincformaldehydeNAD+H2OformateNADHH+Methanediol
Typeheavy metalcarbohydrateamide group,amine group,nucleotideH2Ocarboxyl groupamide group,amine group,nucleotideothers
ChEBI29105
16842
15846
15377
30751
16908
15378

PubChem32051
712
5893
962
22247451
284
18971002
439153
1038

                
1kolA01Bound:2x_ZNUnboundUnbound UnboundUnbound Unbound
1kolB01Bound:2x_ZNUnboundUnbound UnboundUnbound Unbound
1kolA02UnboundUnboundBound:NAD UnboundUnbound Unbound
1kolB02UnboundUnboundBound:NAD UnboundUnbound Unbound

Active-site residues
resource
literature[1],[2]
pdbCatalytic residuesCofactor-binding residues
          
1kolA01SER 48;HIS 51
CYS 46;HIS 67;ASP 169(Catalytic zinc binding);CYS 97;CYS 100;CYS 103;CYS 111(Zinc binding)
1kolB01SER 48;HIS 51
CYS 46;HIS 67;ASP 169(Catalytic zinc binding);CYS 97;CYS 100;CYS 103;CYS 111(Zinc binding)
1kolA02GLU 265
 
1kolB02GLU 265
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Fig.7, p529

references
[1]
PubMed ID12445786
JournalJ Mol Biol
Year2002
Volume324
Pages519-33
AuthorsTanaka N, Kusakabe Y, Ito K, Yoshimoto T, Nakamura KT
TitleCrystal structure of formaldehyde dehydrogenase from Pseudomonas putida: the structural origin of the tightly bound cofactor in nicotinoprotein dehydrogenases.
Related PDB1kol
Related UniProtKBP46154
[2]
PubMed ID12604206
JournalChem Biol Interact
Year2003
Volume143-144
Pages211-8
AuthorsTanaka N, Kusakabe Y, Ito K, Yoshimoto T, Nakamura KT
TitleCrystal structure of glutathione-independent formaldehyde dehydrogenase.

comments
This enzyme belongs to the zinc-containing medium-chain alcohol dehydrogenase (ADH) family. It is homologous to other alcohol dehydrogenases (D00001, D00002, D00018, D00481, D00482, D00490 and D00492 in EzCatDB), sharing a similar active site with them.
This enzyme is glutathione-independent formaldehyde dehydrogenase, whereas its homologous enzyme is glutathione-dependent formaldehyde dehydrogenase (EC 1.1.1.1. & 1.1.1.284; D00018 in EzCatDB) (see [1]).
To this enzyme, NAD(H) is tightly but not covalently bound as a cofactor.
In contrast to the active sites of the homologous enzymes, the active site of this enzyme involves Glu265 from NAD-binding domain in the proton relay system, which is usually composed of the substrate hydroxyl group bound to zinc ion, Ser48, the 2'-hydroxyl group of the NAD ribose and His51 on the catalytic domain. Glu265 is exposed to solvent on the enzyme protein surface.
According to the literature [1], the reaction catalyzed by this enzyme consists of two half-reaction. In the first half-reaction, one aldehyde molecule is oxidized to form a corresponding carboxylate. In the second half-reaction, another aldehyde molecule is reduced to an alcohol.
Thus, this enzyme catalyzes the following reactions:
Oxidation in the first half-reaction:
(A) Addition of water to aldehyde to form hydrated gem-diol (I00152); RCHO + H2O => RCH(OH)2:
(B) Hydride transfer from the hydrated gem-diol to NAD+, forming carboxylate; RCH(OH)2 + NAD+ => RCOOH + NADH:
Reduction in the second half-reaction:
(C) Hydride transfer from NADH to aldehyde, forming alcohol; RCHO + NADH => RCH2OH + NAD+:
### In the case of formaldehyde, R = H.
Although the reactions (B) and (C) must be similar to those by the homologous enzymes, the reaction mechanism of the water addition has not been elucidated yet.

createdupdated
2012-09-272012-10-18


Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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