Dihydrofolate reductase
Details
- Name
- Dihydrofolate reductase
- Synonyms
- 1.5.1.3
- tmrA
- Gene Name
- folA
- Organism
- Escherichia coli (strain K12)
- Amino acid sequence
>lcl|BSEQ0019220|Dihydrofolate reductase MISLIAALAVDRVIGMENAMPWNLPADLAWFKRNTLNKPVIMGRHTWESIGRPLPGRKNI ILSSQPGTDDRVTWVKSVDEAIAACGDVPEIMVIGGGRVYEQFLPKAQKLYLTHIDAEVE GDTHFPDYEPDDWESVFSEFHDADAQNSHSYCFEILERR
- Number of residues
- 159
- Molecular Weight
- 17999.21
- Theoretical pI
- 4.61
- GO Classification
- Functionsdihydrofolate reductase activity / NADP bindingProcessesglycine biosynthetic process / nucleotide biosynthetic process / one-carbon metabolic process / response to antibiotic / response to drug / response to methotrexate / tetrahydrofolate biosynthetic processComponentscytosol
- General Function
- Nadp binding
- Specific Function
- Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
- Pfam Domain Function
- DHFR_1 (PF00186)
- Transmembrane Regions
- Not Available
- Cellular Location
- Not Available
- Gene sequence
>lcl|BSEQ0019221|Dihydrofolate reductase (folA) ATGATCAGTCTGATTGCGGCGTTAGCGGTAGATCGCGTTATCGGCATGGAAAACGCCATG CCGTGGAACCTGCCTGCCGATCTCGCCTGGTTTAAACGCAACACCTTAAATAAACCCGTG ATTATGGGCCGCCATACCTGGGAATCAATCGGTCGTCCGTTGCCAGGACGCAAAAATATT ATCCTCAGCAGTCAACCGGGTACGGACGATCGCGTAACGTGGGTGAAGTCGGTGGATGAA GCCATCGCGGCGTGTGGTGACGTACCAGAAATCATGGTGATTGGCGGCGGTCGCGTTTAT GAACAGTTCTTGCCAAAAGCGCAAAAACTGTATCTGACGCATATCGACGCAGAAGTGGAA GGCGACACCCATTTCCCGGATTACGAGCCGGATGACTGGGAATCGGTATTCAGCGAATTC CACGATGCTGATGCGCAGAACTCTCACAGCTATTGCTTTGAGATTCTGGAGCGGCGGTAA
- Chromosome Location
- Not Available
- Locus
- Not Available
- External Identifiers
Resource Link UniProtKB ID P0ABQ4 UniProtKB Entry Name DYR_ECOLI GenBank Protein ID 146006 GenBank Gene ID J01609 - General References
- Stone D, Phillips AW, Burchall JJ: The amino-acid sequence of the dihydrofolate reductase of a trimethoprim-resistant strain of Escherichia coli. Eur J Biochem. 1977 Feb;72(3):613-24. [Article]
- Bennett CD, Rodkey JA, Sondey JM, Hirschmann R: Dihydrofolate reductase: the amino acid sequence of the enzyme from a methotrexate-resistant mutant of Escherichia coli. Biochemistry. 1978 Apr 4;17(7):1328-37. [Article]
- Smith DR, Calvo JM: Nucleotide sequence of the E coli gene coding for dihydrofolate reductase. Nucleic Acids Res. 1980 May 24;8(10):2255-74. [Article]
- Baccanari DP, Stone D, Kuyper L: Effect of a single amino acid substitution on Escherichia coli dihydrofolate reductase catalysis and ligand binding. J Biol Chem. 1981 Feb 25;256(4):1738-47. [Article]
- Flensburg J, Skold O: Massive overproduction of dihydrofolate reductase in bacteria as a response to the use of trimethoprim. Eur J Biochem. 1987 Feb 2;162(3):473-6. [Article]
- Yura T, Mori H, Nagai H, Nagata T, Ishihama A, Fujita N, Isono K, Mizobuchi K, Nakata A: Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region. Nucleic Acids Res. 1992 Jul 11;20(13):3305-8. [Article]
- Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. [Article]
- Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. Epub 2006 Feb 21. [Article]
- VanBogelen RA, Abshire KZ, Moldover B, Olson ER, Neidhardt FC: Escherichia coli proteome analysis using the gene-protein database. Electrophoresis. 1997 Aug;18(8):1243-51. [Article]
- Filman DJ, Bolin JT, Matthews DA, Kraut J: Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7 A resolution. II. Environment of bound NADPH and implications for catalysis. J Biol Chem. 1982 Nov 25;257(22):13663-72. [Article]
- Bystroff C, Oatley SJ, Kraut J: Crystal structures of Escherichia coli dihydrofolate reductase: the NADP+ holoenzyme and the folate.NADP+ ternary complex. Substrate binding and a model for the transition state. Biochemistry. 1990 Apr 3;29(13):3263-77. [Article]
- Bystroff C, Kraut J: Crystal structure of unliganded Escherichia coli dihydrofolate reductase. Ligand-induced conformational changes and cooperativity in binding. Biochemistry. 1991 Feb 26;30(8):2227-39. [Article]
- Reyes VM, Sawaya MR, Brown KA, Kraut J: Isomorphous crystal structures of Escherichia coli dihydrofolate reductase complexed with folate, 5-deazafolate, and 5,10-dideazatetrahydrofolate: mechanistic implications. Biochemistry. 1995 Feb 28;34(8):2710-23. [Article]
- Lee H, Reyes VM, Kraut J: Crystal structures of Escherichia coli dihydrofolate reductase complexed with 5-formyltetrahydrofolate (folinic acid) in two space groups: evidence for enolization of pteridine O4. Biochemistry. 1996 Jun 4;35(22):7012-20. [Article]
- Sawaya MR, Kraut J: Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence. Biochemistry. 1997 Jan 21;36(3):586-603. [Article]
- Iwakura M, Maki K, Takahashi H, Takenawa T, Yokota A, Katayanagi K, Kamiyama T, Gekko K: Evolutional design of a hyperactive cysteine- and methionine-free mutant of Escherichia coli dihydrofolate reductase. J Biol Chem. 2006 May 12;281(19):13234-46. Epub 2006 Mar 1. [Article]
- Summerfield RL, Daigle DM, Mayer S, Mallik D, Hughes DW, Jackson SG, Sulek M, Organ MG, Brown ED, Junop MS: A 2.13 A structure of E. coli dihydrofolate reductase bound to a novel competitive inhibitor reveals a new binding surface involving the M20 loop region. J Med Chem. 2006 Nov 30;49(24):6977-86. [Article]
- Bennett B, Langan P, Coates L, Mustyakimov M, Schoenborn B, Howell EE, Dealwis C: Neutron diffraction studies of Escherichia coli dihydrofolate reductase complexed with methotrexate. Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18493-8. Epub 2006 Nov 27. [Article]
- Bennett BC, Wan Q, Ahmad MF, Langan P, Dealwis CG: X-ray structure of the ternary MTX.NADPH complex of the anthrax dihydrofolate reductase: a pharmacophore for dual-site inhibitor design. J Struct Biol. 2009 May;166(2):162-71. [Article]
Drug Relations
- Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details DB00440 Trimethoprim approved, vet_approved yes inhibitor Details DB02015 Dihydrofolic Acid experimental unknown Details DB02363 2'-Monophosphoadenosine-5'-Diphosphate experimental unknown Details DB03461 Nicotinamide adenine dinucleotide phosphate experimental unknown Details DB12769 Lometrexol investigational unknown Details DB07262 1-{[N-(1-Imino-guanidino-methyl)]sulfanylmethyl}-3-trifluoromethyl-benzene experimental unknown Details