DB code: D00615

CATH domain	3.90.180.10 : Quinone Oxidoreductase; Chain A, domain 1	Catalytic domain
CATH 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)
3.40.50.720 : 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
3.90.180.10 : Quinone Oxidoreductase; Chain A, domain 1	D00001 D00002 D00018 D00048 D00481 D00482 D00490 D00492

CATH domain

Related DB codes (homologues)

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

3.90.180.10 : Quinone Oxidoreductase; Chain A, domain 1

D00001 D00002 D00018 D00048 D00481 D00482 D00490 D00492

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	Formaldehyde + NAD(+) + H(2)O = formate + NADH. An alcohol + NAD(+) = an aldehyde or ketone + NADH.	Homotetramer.		Binds 2 zinc ions per subunit.

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

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 29105	16842 16842	15846 15846	15377 15377	30751 30751	16908 16908	15378 15378
PubChem	32051 32051	712 712	5893 5893	22247451 962 22247451 962	18971002 284 18971002 284	439153 439153	1038 1038

1kolA01	Bound:2x_ZN	Unbound	Unbound		Unbound	Unbound		Unbound
1kolB01	Bound:2x_ZN	Unbound	Unbound		Unbound	Unbound		Unbound
1kolA02	Unbound	Unbound	Bound:NAD		Unbound	Unbound		Unbound
1kolB02	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	SER 48;HIS 51	CYS 46;HIS 67;ASP 169(Catalytic zinc binding);CYS 97;CYS 100;CYS 103;CYS 111(Zinc binding)
1kolB01	SER 48;HIS 51	CYS 46;HIS 67;ASP 169(Catalytic zinc binding);CYS 97;CYS 100;CYS 103;CYS 111(Zinc binding)
1kolA02	GLU 265
1kolB02	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.

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