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Quadruple mutant (N51I+C59R+S108N+I164L) plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with P218 and NADPH

Source organism: Plasmodium falciparum VS/1
Biochemical function: transferase activity, transferring one-carbon groups
Biological process: tetrahydrofolate biosynthetic process
Cellular component: cytosol

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EC 2.1.1.45: Thymidylate synthase

Reaction catalysed:
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
Systematic name:
5,10-methylenetetrahydrofolate:dUMP C-methyltransferase
Alternative Name(s):
  • Methylenetetrahydrofolate:dUMP C-methyltransferase
  • TMP synthetase
  • Thymidylate synthetase
  • dTMP synthase

EC 1.5.1.3: Dihydrofolate reductase

Reaction catalysed:
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
Systematic name:
5,6,7,8-tetrahydrofolate:NADP(+) oxidoreductase
Alternative Name(s):
  • 7,8-dihydrofolate reductase
  • DHFR
  • Dihydrofolate reductase:thymidylate synthase
  • Dihydrofolic acid reductase
  • Dihydrofolic reductase
  • Folic acid reductase
  • Folic reductase
  • NADPH-dihydrofolate reductase
  • Pteridine reductase:dihydrofolate reductase
  • Tetrahydrofolate dehydrogenase
  • Thymidylate synthetase-dihydrofolate reductase

GO terms

Sequence families

Pfam Protein families (Pfam)
PF00303
Domain description: Thymidylate synthase
Occurring in:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
The deposited structure of PDB entry 4dp3 contains 2 copies of Pfam domain PF00303 (Thymidylate synthase) in Bifunctional dihydrofolate reductase-thymidylate synthase. Showing 1 copy in chain A.

PF00186
Domain description: Dihydrofolate reductase
Occurring in:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
The deposited structure of PDB entry 4dp3 contains 2 copies of Pfam domain PF00186 (Dihydrofolate reductase) in Bifunctional dihydrofolate reductase-thymidylate synthase. Showing 1 copy in chain A.

InterPro InterPro annotations
IPR000398
Domain description: Thymidylate synthase
Occurring in:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
IPR001796
Domain description: Dihydrofolate reductase domain
Occurring in:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
IPR023451
Domain description: Thymidylate synthase/dCMP hydroxymethylase domain
Occurring in:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
IPR036926
Domain description: Thymidylate synthase/dCMP hydroxymethylase superfamily
Occurring in:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
IPR024072
Domain description: Dihydrofolate reductase-like domain superfamily
Occurring in:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
IPR020940
Domain description: Thymidylate synthase, active site
Occurring in:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
IPR045097
Domain description: Thymidylate synthase/dCMP hydroxymethylase
Occurring in:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
IPR017925
Domain description: Dihydrofolate reductase conserved site
Occurring in:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
IPR012262
Domain description: Bifunctional dihydrofolate reductase/thymidylate synthase
Occurring in:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase

Structure domains

CATH CATH domains
3.30.572.10
Class: Alpha Beta
Architecture: 2-Layer Sandwich
Topology: Thymidylate Synthase; Chain A
Homology: Thymidylate synthase/dCMP hydroxymethylase domain
Occurring in:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
The deposited structure of PDB entry 4dp3 contains 2 copies of CATH domain 3.30.572.10 (Thymidylate Synthase; Chain A) in Bifunctional dihydrofolate reductase-thymidylate synthase. Showing 1 copy in chain A.
6.10.250.2210
Class: Special
Architecture: Helix non-globular
Topology: Single alpha-helices involved in coiled-coils or other helix-helix interfaces
Homology: Single alpha-helices involved in coiled-coils or other helix-helix interfaces
Occurring in:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
The deposited structure of PDB entry 4dp3 contains 2 copies of CATH domain 6.10.250.2210 (Single alpha-helices involved in coiled-coils or other helix-helix interfaces) in Bifunctional dihydrofolate reductase-thymidylate synthase. Showing 1 copy in chain A.
3.40.430.10
Class: Alpha Beta
Architecture: 3-Layer(aba) Sandwich
Topology: Dihydrofolate Reductase, subunit A
Homology: Dihydrofolate Reductase, subunit A
Occurring in:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
The deposited structure of PDB entry 4dp3 contains 2 copies of CATH domain 3.40.430.10 (Dihydrofolate Reductase, subunit A) in Bifunctional dihydrofolate reductase-thymidylate synthase. Showing 1 copy in chain A.

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