Overview for MACiE Entry M0120
EC Number: 22.214.171.124 (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).
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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 1||NAD(P) eliminates a hydride ion, which adds to FAD with concomitant deprotonation of water at the N1.|
|Step 2||The 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 3||Water 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
||Location of Function
Organic Cofactors for M0120
- 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.
- 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.
Homologue information for M0120 (1zp3)
MACiE Homologues (within the PDB)
MACiE Homologues (within UniprotKB/SwissProt)
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