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Overview for MACiE Entry M0120

Version history

General Information

EC Number: 1.5.1.20 (A member of the Oxidoreductases, Acting on the CH-NH group of donors, With NAD+ or NADP+ as acceptor)

Enzyme Name: methylenetetrahydrofolate reductase [NAD(P)H]

Biological Species: Escherichia coli (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

  • P0AEZ1 - 5,10-methylenetetrahydrofolate reductase

Representative PDB Code: 1zp3 - E. COLI METHYLENETETRAHYDROFOLATE REDUCTASE (OXIDIZED) (Resolution = 1.85 Å).

Catalytic CATH Codes:

"Other" CATH Codes:

Display structure information

Overall Reaction:

Image of NADPH

Image of proton

Image of 5,10-methylenetetrahydrofolate

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Image of NADP

Image of 5-methyltetrahydrofolate

NADPH
C00005
CHEBI:16474
proton
C00080
CHEBI:24636
5,10-methylenetetrahydrofolate
C00143
CHEBI:15636
NADP
C00006
CHEBI:18009
5-methyltetrahydrofolate
C00440
CHEBI:18608

Overall Comment: NAD(P) and 5,10-methylenetetrahydrofolate both bind at the si face of the reduced FAD which is consistent with a ping-pong Bi-Bi mechanism. This is also supported by steady state and transient kinetic studies.


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Stepwise Description of the Reaction

Step 1NAD(P) eliminates a hydride ion, which adds to FAD with concomitant deprotonation of water at the N1.
Step 2The substrate initiates the cleavage of the five-membered ring, forming the 5-iminium cation intermediate, with concomitant deprotonation of water through a proton relay chain of water, Glu28, His273 and Ser26.
Step 3Water deprotonates FAD, causing the elimination of a hydride which is added to the 5-iminium carbon of the intermediate.

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Catalytic Residues Involved

Type Number Chain Location of Function
Ser 26 A Side Chain
Glu 28 A Side Chain
Asp 120 A Side Chain
His 273 A Side Chain

Organic Cofactors for M0120

Type Identity Chain
FAD FAD 395 Overview

References

  1. E. E. Trimmer et al. (2001), Biochemistry, 40, 6216-6226. Folate activation and catalysis in methylenetetrahydrofolate reductase from Escherichia coli: roles for aspartate 120 and glutamate 28.
    Medline: 11371182
  2. R. Pejchal et al. (2005), Biochemistry, 44, 11447-11457. Structures of NADH and CH3-H4folate complexes of Escherichia coli methylenetetrahydrofolate reductase reveal a spartan strategy for a ping-pong reaction.
    Medline: 16114881

Homologue information for M0120 (1zp3)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ

GOA logo
methylenetetrahydrofolate reductase (NAD(P)H) activity (molecular function)
methionine metabolic process (biological process)
methionine biosynthetic process (biological process)
oxidation-reduction process (biological process)
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