spacer

Overview for MACiE Entry M0112

Version history

General Information

EC Number: 1.5.1.3 (A member of the Oxidoreductases, Acting on the CH-NH group of donors, With NAD+ or NADP+ as acceptor)

Enzyme Name: dihydrofolate reductase

Biological Species: Lactobacillus casei (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

  • P00381 - Dihydrofolate reductase

Representative PDB Code: 3dfr - CRYSTAL STRUCTURES OF ESCHERICHIA COLI AND LACTOBACILLUSCASEI DIHYDROFOLATE REDUCTASE REFINED AT 1.7 ANGSTROMSRESOLUTION. I. GENERAL FEATURES AND BINDING OF METHOTREXATE (Resolution = 1.70 Å).

Catalytic CATH Codes:

Display structure information

Overall Reaction:

Image of NADPH

Image of proton

Image of dihydrofolate

right arrow

Image of tetrahydrofolate

Image of NADP

NADPH
C00005
CHEBI:16474
proton
C00080
CHEBI:24636
dihydrofolate
C00415
CHEBI:15633
tetrahydrofolate
C00101
CHEBI:20506
NADP
C00006
CHEBI:18009

View similar reactions


Stepwise Description of the Reaction

Step 1The dihydrofolate substrate undergoes a tautomerisation reaction, resulting in the deprotonation of water.
Step 2NADP eliminates a hydride ion, which adds to the C6 of the pterin ring, the N5 of the pterin ring deprotonates water, which deprotonates a second water, deprotonating the hydroxyl, which regenerates the correct tautomeric form of the tetrahydrofolate product.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Trp 21 A Side Chain
Asp 26 A Side Chain
Thr 116 A Side Chain

References

  1. M. G. Casarotto et al. (1999), Biochemistry, 38, 8038-8044. Direct measurement of the pKa of aspartic acid 26 in Lactobacillus casei dihydrofolate reductase: implications for the catalytic mechanism.
    Medline: 10387048
  2. P. Shrimpton et al. (2002), Protein Sci., 11, 1442-1451. Role of water in the catalytic cycle of E. coli dihydrofolate reductase.
    Medline: 12021443

Homologue information for M0112 (3dfr)

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
dihydrofolate reductase activity (molecular function)
glycine biosynthetic process (biological process)
one-carbon metabolic process (biological process)
nucleotide biosynthetic process (biological process)
oxidoreductase activity (molecular function)
response to methotrexate (biological process)
response to antibiotic (biological process)
NADP binding (molecular function)
oxidation-reduction process (biological process)
spacer
spacer