DB code: D00615

CATH domain 3.90.180.10 : Quinone Oxidoreductase; Chain A, domain 1 Catalytic domain
3.40.50.720 : Rossmann fold Catalytic domain
E.C. 1.2.1.46
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.90.180.10 : Quinone Oxidoreductase; Chain A, domain 1 D00001 D00002 D00018 D00048 D00481 D00482 D00490 D00492
3.40.50.720 : Rossmann fold S00543 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
P46154 Glutathione-independent formaldehyde dehydrogenase
FALDH
FDH
EC 1.2.1.46
PF08240 (ADH_N)
PF01262 (AlaDh_PNT_C)
[Graphical View]

KEGG enzyme name
Formaldehyde dehydrogenase
NAD+-linked formaldehyde dehydrogenase
NAD+-dependent formaldehyde dehydrogenase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P46154 FADH_PSEPU An alcohol + NAD(+) = an aldehyde or ketone + NADH. Formaldehyde + NAD(+) + H(2)O = formate + NADH. Homotetramer. Binds 2 zinc ions per subunit.

KEGG Pathways
Map code Pathways E.C.
MAP00680 Methane metabolism
MAP00625 Chloroalkane and chloroalkene degradation

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C00067 C00003 C00001 C00058 C00004 C00080 I00152
E.C.
Compound Zinc formaldehyde NAD+ H2O formate NADH H+ Methanediol
Type heavy metal carbohydrate amide group,amine group,nucleotide H2O carboxyl group amide group,amine group,nucleotide others
ChEBI 29105
16842
15846
15377
30751
16908
15378
PubChem 32051
712
5893
962
22247451
284
18971002
439153
1038
1kolA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Unbound Unbound Unbound Unbound Unbound
1kolB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Unbound Unbound Unbound Unbound Unbound
1kolA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAD Unbound Unbound Unbound
1kolB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAD Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature[1],[2]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1kolA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 48;HIS 51 CYS 46;HIS 67;ASP 169(Catalytic zinc binding);CYS 97;CYS 100;CYS 103;CYS 111(Zinc binding)
1kolB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 48;HIS 51 CYS 46;HIS 67;ASP 169(Catalytic zinc binding);CYS 97;CYS 100;CYS 103;CYS 111(Zinc binding)
1kolA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 265
1kolB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 265

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
Fig.7, p529

References
[1]
Resource
Comments
Medline ID
PubMed ID 12445786
Journal J Mol Biol
Year 2002
Volume 324
Pages 519-33
Authors Tanaka N, Kusakabe Y, Ito K, Yoshimoto T, Nakamura KT
Title Crystal structure of formaldehyde dehydrogenase from Pseudomonas putida: the structural origin of the tightly bound cofactor in nicotinoprotein dehydrogenases.
Related PDB 1kol
Related UniProtKB P46154
[2]
Resource
Comments
Medline ID
PubMed ID 12604206
Journal Chem Biol Interact
Year 2003
Volume 143-144
Pages 211-8
Authors Tanaka N, Kusakabe Y, Ito K, Yoshimoto T, Nakamura KT
Title Crystal structure of glutathione-independent formaldehyde dehydrogenase.
Related PDB
Related UniProtKB

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.

Created Updated
2012-09-27 2012-10-18