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EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1vie

E.C. namedihydrofolate reductase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz)
CSA Homologues of 1vie1vif,2gqv,2p4t,2rh2,2rk1,2rk2,
CSA Entries With UniProtID P00383
CSA Entries With EC Number
PDBe Entry 1vie
PDBSum Entry 1vie
MACiE Entry 1vie

Literature Report

IntroductionR67-plasmid encoded dihydrofolate reductase (R67-DHFR) from Escherichia coli catalyses the reduction of 7,8-dihydrofolate (DHF) to 5,6,7,8-tetrahydrofolate (THF) in the presence of NADPH. It is one of the smallest enzymes known to self-assemble into an active quaternary structure. The tetramer has an unusual pore, 25 angstroms in length that passes through the middle of the molecule and out the other side. R67-DHFR has 222 symmetry, and has a distinctive 'one site fits both' substrate and cofactor.
MechansimThe mechanism of R67-DHFR relies on a pre-protonated form of DHF being the substrate. The substrate then accepts a hydride from NADPH to form the product, THF. The catalytic residues Tyr 69, Ile 68 and Gln 67 destabilise the ground state. Lys 32 is involved in stabilising the transition state.

Catalytic Sites for 1vie

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
IleA6868macie:sideChainIle 68 acts to destabilise the ground state.
LysA3232macie:sideChainThe positively charged sidechain of Lys 32 helps to stabilise the negatively charged intermediate.
TyrA6969macie:sideChainTyr 69 acts to destabilise the ground state.
GlnA6767macie:sideChainGln 67 acts to destabilise the ground state of the substrate.

Literature References

Notes:It is not exactly known how these residues stabilise the transition state or destabilise the ground state.
Howell EE.
Searching sequence space: two different approaches to dihydrofolate reductase catalysis.
Chembiochem 2005 6 590-600
PubMed: 15812782
Strader MB
Role of S65, Q67, I68, and Y69 residues in homotetrameric R67 dihydrofolate reductase.
Biochemistry 2001 40 11344-11352
PubMed: 11560482