Dihydrofolate reductase

DHFR
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesDHFR, DHFRP1, DYR, dihydrofolate reductase
External IDsOMIM: 126060; MGI: 94890; HomoloGene: 56470; GeneCards: DHFR; OMA:DHFR - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000791
NM_001290354
NM_001290357

NM_010049

RefSeq (protein)

NP_000782
NP_001277283
NP_001277286

NP_034179

Location (UCSC)Chr 5: 80.63 – 80.65 MbChr 13: 92.49 – 92.53 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as an electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in one-carbon transfer chemistry. In humans, the DHFR enzyme is encoded by the DHFR gene.[5][6] It is found in the q14.1 region of chromosome 5.[7]

There are two structural classes of DHFR, evolutionarily unrelated to each other. The former is usually just called DHFR and is found in bacterial chromosomes and animals. In bacteria, however, antibiotic pressure has caused this class to evolve different patterns of binding diaminoheterocyclic molecules, leading to many "types" named under this class, while mammalian ones remain highly similar.[8] The latter (type II), represented by the plastid-encoded R67, is a tiny enzyme that works by forming a homotetramer.[9]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000228716Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021707Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Chen MJ, Shimada T, Moulton AD, Harrison M, Nienhuis AW (December 1982). "Intronless human dihydrofolate reductase genes are derived from processed RNA molecules". Proceedings of the National Academy of Sciences of the United States of America. 79 (23): 7435–9. Bibcode:1982PNAS...79.7435C. doi:10.1073/pnas.79.23.7435. PMC 347354. PMID 6961421.
  6. ^ Chen MJ, Shimada T, Moulton AD, Cline A, Humphries RK, Maizel J, Nienhuis AW (March 1984). "The functional human dihydrofolate reductase gene". The Journal of Biological Chemistry. 259 (6): 3933–43. doi:10.1016/S0021-9258(17)43186-3. PMID 6323448.
  7. ^ "DHFR dihydrofolate reductase [Homo sapiens (human)]". Gene - NCBI. Retrieved 21 February 2023.
  8. ^ Smith SL, Patrick P, Stone D, Phillips AW, Burchall JJ (November 1979). "Porcine liver dihydrofolate reductase. Purification, properties, and amino acid sequence". The Journal of Biological Chemistry. 254 (22): 11475–84. doi:10.1016/S0021-9258(19)86510-9. PMID 500653.
  9. ^ Krahn JM, Jackson MR, DeRose EF, Howell EE, London RE (25 December 2007). "Crystal structure of a type II dihydrofolate reductase catalytic ternary complex". Biochemistry. 46 (51): 14878–88. doi:10.1021/bi701532r. PMC 3743094. PMID 18052202.