DB code: S00238

CATH domain 3.20.20.220 : TIM Barrel Catalytic domain
E.C. 1.5.1.20
CSA 1b5t
M-CSA 1b5t
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P0AEZ1 5,10-methylenetetrahydrofolate reductase
EC 1.5.1.20
NP_418376.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_491510.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF02219 (MTHFR)
[Graphical View]

KEGG enzyme name
methylenetetrahydrofolate reductase [NAD(P)H]
methylenetetrahydrofolate (reduced nicotinamide adenine dinucleotidephosphate) reductase
5,10-methylenetetrahydrofolate reductase (NADPH)
5,10-methylenetetrahydrofolic acid reductase
5,10-CH2-H4folate reductase
methylenetetrahydrofolate reductase (NADPH2)
5-methyltetrahydrofolate:NAD+ oxidoreductase
5-methyltetrahydrofolate:NAD+ oxidoreductase
methylenetetrahydrofolate (reduced riboflavin adenine dinucleotide)reductase
5,10-methylenetetrahydrofolate reductase
methylenetetrahydrofolate reductase
N5,10-methylenetetrahydrofolate reductase
5,10-methylenetetrahydropteroylglutamate reductase
N5,N10-methylenetetrahydrofolate reductase
methylenetetrahydrofolic acid reductase
5-methyltetrahydrofolate:(acceptor) oxidoreductase (incorrect)
5,10-methylenetetrahydrofolate reductase (FADH2)
MetF
methylenetetrahydrofolate reductase (NADPH)
5-methyltetrahydrofolate:NADP+ oxidoreductase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P0AEZ1 METF_ECOLI 5-methyltetrahydrofolate + NAD(P)(+) = 5,10- methylenetetrahydrofolate + NAD(P)H. Homotetramer. FAD.

KEGG Pathways
Map code Pathways E.C.
MAP00670 One carbon pool by folate
MAP00680 Methane metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00016 C00703 C00440 C00003 C00006 C00143 C00004 C00005
E.C.
Compound FAD Hg2+ 5-Methyltetrahydrofolate NAD+ NADP+ 5,10-Methylenetetrahydrofolate NADH NADPH
Type amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,nucleotide heavy metal amino acids,amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carboxyl group amide group,amine group,nucleotide amide group,amine group,nucleotide amino acids,amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carboxyl group amide group,amine group,nucleotide amide group,amine group,nucleotide
ChEBI 16238
 16238
 		16793
 16793
 		15641
 15641
 		15846
 15846
 		18009
 18009
 		16908
 16908
 		16474
 16474
PubChem 643975
 643975
 		26623
 26623
 		439234
 444412
 439234
 444412
 		5893
 5893
 		5886
 5886
 		439175
 439175
 		439153
 439153
 		5884
 5884
1b5tA Bound:FAD Bound:_HG Unbound Unbound Unbound Unbound Unbound Unbound
1b5tB Bound:FAD Bound:_HG Unbound Unbound Unbound Unbound Unbound Unbound
1b5tC Bound:FAD Bound:_HG Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
PDB;1b5t & literature [7]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1b5tA GLU 28;ASP 120 CYS 91;ILE 92;ARG 118;MET 130(Mercury binding)
1b5tB GLU 28;ASP 120 CYS 91;ILE 92;ARG 118;MET 130(Mercury binding)
1b5tC GLU 28;ASP 120 CYS 91;ILE 92;ARG 118; (Mercury binding) invisible M130

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
Scheme 1, Fig.1, p.6223-6225

References
[1]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS)
Medline ID 99215588
PubMed ID 10201405
Journal Nat Struct Biol
Year 1999
Volume 6
Pages 359-65
Authors Guenther BD, Sheppard CA, Tran P, Rozen R, Matthews RG, Ludwig ML
Title The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia.
Related PDB 1b5t
Related UniProtKB P0AEZ1
[2]
Resource
Comments
Medline ID
PubMed ID 11086190
Journal J Biochem Biophys Methods
Year 2000
Volume 46
Pages 11-20
Authors Sobti P, Rothenberg SP, Quadros EV
Title Radioenzymatic assay for reductive catalysis of N(5)N(10)-methylenetetrahydrofolate by methylenetetrahydrofolate reductase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 11371182
Journal Biochemistry
Year 2001
Volume 40
Pages 6216-26
Authors Trimmer EE, Ballou DP, Ludwig ML, Matthews RG
Title Folate activation and catalysis in methylenetetrahydrofolate reductase from Escherichia coli: roles for aspartate 120 and glutamate 28.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 11371181
Journal Biochemistry
Year 2001
Volume 40
Pages 6205-15
Authors Trimmer EE, Ballou DP, Matthews RG
Title Methylenetetrahydrofolate reductase from Escherichia coli: elucidation of the kinetic mechanism by steady-state and rapid-reaction studies.
Related PDB
Related UniProtKB

Comments
The E.C. was transferred from 1.7.99.5 to 1.5.1.20.
Although mercury is annotated as a cofactor, it is not clear how it functions in the active site.

Created Updated
2004-08-04 2009-02-26