Dihydrofolate reductase

Details

Name
Dihydrofolate reductase
Synonyms
  • 1.5.1.3
  • dhfR
Gene Name
folA
Organism
Lactobacillus casei
Amino acid sequence
>lcl|BSEQ0011145|Dihydrofolate reductase
MTAFLWAQDRDGLIGKDGHLPWHLPDDLHYFRAQTVGKIMVVGRRTYESFPKRPLPERTN
VVLTHQEDYQAQGAVVVHDVAAVFAYAKQHPDQELVIAGGAQIFTAFKDDVDTLLVTRLA
GSFEGDTKMIPLNWDDFTKVSSRTVEDTNPALTHTYEVWQKKA
Number of residues
163
Molecular Weight
18438.73
Theoretical pI
6.14
GO Classification
Functions
dihydrofolate reductase activity / NADP binding
Processes
glycine biosynthetic process / nucleotide biosynthetic process / one-carbon metabolic process / response to antibiotic / response to methotrexate / tetrahydrofolate biosynthetic process
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
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0003202|492 bp
ATGACCGCATTTTTATGGGCACAGGATCGCGATGGCTTAATTGGCAAAGATGGTCATTTG
CCATGGCATTTACCGGATGATTTACATTATTTCCGGGCGCAGACAGTTGGTAAGATCATG
GTCGTTGGTCGGCGCACCTATGAAAGTTTTCCTAAACGTCCTTTACCTGAGCGAACCAAT
GTTGTTTTGACCCATCAGGAAGACTATCAAGCGCAAGGTGCCGTGGTCGTGCATGATGTT
GCGGCGGTTTTTGCTTATGCTAAGCAGCATCCCGATCAGGAACTGGTCATTGCTGGCGGT
GCACAGATCTTTACGGCTTTTAAAGATGATGTCGATACGTTACTGGTAACACGTTTGGCT
GGCAGTTTTGAAGGCGATACGAAAATGATTCCATTAAACTGGGATGATTTTACCAAAGTC
TCCAGCCGCACCGTTGAAGATACCAATCCGGCGCTGACGCACACTTATGAGGTTTGGCAA
AAGAAGGCTTAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP00381
UniProtKB Entry NameDYR_LACCA
GenBank Protein ID149540
GenBank Gene IDM10922
General References
  1. Andrews J, Clore GM, Davies RW, Gronenborn AM, Gronenborn B, Kalderon D, Papadopoulos PC, Schafer S, Sims PF, Stancombe R: Nucleotide sequence of the dihydrofolate reductase gene of methotrexate-resistant Lactobacillus casei. Gene. 1985;35(1-2):217-22. [PubMed:3928445]
  2. Freisheim JH, Bitar KG, Reddy AV, Blankenship DT: Dihydrofolate reductase from amethopterin-resistant Lactobacillus casei. Sequences of the cyanogen bromide peptides and complete sequences of the enzyme. J Biol Chem. 1978 Sep 25;253(18):6437-44. [PubMed:98527]
  3. Batley KE, Morris HR: Dihydrofolate reductase from Lactobacillus casei: N-terminal sequence and comparison with the substrate binding region of other reductases. Biochem Biophys Res Commun. 1977 Apr 25;75(4):1010-4. [PubMed:405008]
  4. 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. [PubMed:6815179]
  5. Carr MD, Birdsall B, Frenkiel TA, Bauer CJ, Jimenez-Barbero J, Polshakov VI, McCormick JE, Roberts GC, Feeney J: Dihydrofolate reductase: sequential resonance assignments using 2D and 3D NMR and secondary structure determination in solution. Biochemistry. 1991 Jun 25;30(25):6330-41. [PubMed:1905571]
  6. Morgan WD, Birdsall B, Polshakov VI, Sali D, Kompis I, Feeney J: Solution structure of a brodimoprim analogue in its complex with Lactobacillus casei dihydrofolate reductase. Biochemistry. 1995 Sep 19;34(37):11690-702. [PubMed:7547901]
  7. Gargaro AR, Soteriou A, Frenkiel TA, Bauer CJ, Birdsall B, Polshakov VI, Barsukov IL, Roberts GC, Feeney J: The solution structure of the complex of Lactobacillus casei dihydrofolate reductase with methotrexate. J Mol Biol. 1998 Mar 20;277(1):119-34. [PubMed:9514736]
  8. Polshakov VI, Birdsall B, Frenkiel TA, Gargaro AR, Feeney J: Structure and dynamics in solution of the complex of Lactobacillus casei dihydrofolate reductase with the new lipophilic antifolate drug trimetrexate. Protein Sci. 1999 Mar;8(3):467-81. [PubMed:10091649]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02809Brodimoprim-4,6-DicarboxylateexperimentalunknownDetails
DB031252,4-Diamino-5-(3,4,5-Trimethoxy-Benzyl)-Pyrimidin-1-IumexperimentalunknownDetails