Dihydrofolate reductase

Details

Name
Dihydrofolate reductase
Synonyms
  • 1.5.1.3
  • dfrD
Gene Name
dfrA
Organism
Bacillus anthracis
Amino acid sequence
>lcl|BSEQ0012961|Dihydrofolate reductase
MIVSFMVAMDENRVIGKDNNLPWRLPSELQYVKKTTMGHPLIMGRKNYEAIGRPLPGRRN
IIVTRNEGYHVEGCEVAHSVEEVFELCKNEEEIFIFGGAQIYDLFLPYVDKLYITKIHHA
FEGDTFFPEMDMTNWKEVFVEKGLTDEKNPYTYYYHVYEKQQ
Number of residues
162
Molecular Weight
19124.795
Theoretical pI
5.3
GO Classification
Functions
dihydrofolate reductase activity / metal ion binding / NADP binding
Processes
glycine biosynthetic process / nucleotide biosynthetic process / one-carbon metabolic process / 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|BSEQ0012962|Dihydrofolate reductase (dfrA)
ATGATAGTTTCATTTATGGTCGCAATGGACGAAAATAGAGTAATTGGTAAAGATAATAAT
TTACCTTGGCGTTTACCGAGTGAATTGCAGTATGTAAAGAAAACAACGATGGGTCACCCG
CTTATTATGGGAAGAAAAAACTATGAAGCGATTGGTAGACCACTGCCTGGAAGACGTAAT
ATTATTGTAACTCGCAATGAAGGATATCATGTTGAAGGCTGTGAAGTAGCACATTCTGTA
GAAGAAGTGTTTGAGCTATGCAAAAATGAAGAAGAGATCTTTATTTTTGGCGGAGCACAA
ATTTATGATCTCTTTTTACCTTACGTAGACAAGTTATATATAACAAAAATCCATCATGCA
TTTGAAGGAGATACATTTTTCCCAGAAATGGATATGACAAATTGGAAAGAAGTTTTTGTT
GAAAAAGGTTTAACGGATGAAAAAAATCCGTATACGTATTATTACCATGTATATGAGAAA
CAACAATAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ81R22
UniProtKB Entry NameQ81R22_BACAN
GenBank Protein ID30253517
GenBank Gene IDAE016879
General References
  1. Bennett BC, Xu H, Simmerman RF, Lee RE, Dealwis CG: Crystal structure of the anthrax drug target, Bacillus anthracis dihydrofolate reductase. J Med Chem. 2007 Sep 6;50(18):4374-81. Epub 2007 Aug 14. [Article]
  2. Beierlein JM, Frey KM, Bolstad DB, Pelphrey PM, Joska TM, Smith AE, Priestley ND, Wright DL, Anderson AC: Synthetic and crystallographic studies of a new inhibitor series targeting Bacillus anthracis dihydrofolate reductase. J Med Chem. 2008 Dec 11;51(23):7532-40. doi: 10.1021/jm800776a. [Article]
  3. Bourne CR, Bunce RA, Bourne PC, Berlin KD, Barrow EW, Barrow WW: Crystal structure of Bacillus anthracis dihydrofolate reductase with the dihydrophthalazine-based trimethoprim derivative RAB1 provides a structural explanation of potency and selectivity. Antimicrob Agents Chemother. 2009 Jul;53(7):3065-73. doi: 10.1128/AAC.01666-08. Epub 2009 Apr 13. [Article]
  4. Beierlein JM, Deshmukh L, Frey KM, Vinogradova O, Anderson AC: The solution structure of Bacillus anthracis dihydrofolate reductase yields insight into the analysis of structure-activity relationships for novel inhibitors. Biochemistry. 2009 May 19;48(19):4100-8. doi: 10.1021/bi802319w. [Article]
  5. Ravel J, Jiang L, Stanley ST, Wilson MR, Decker RS, Read TD, Worsham P, Keim PS, Salzberg SL, Fraser-Liggett CM, Rasko DA: The complete genome sequence of Bacillus anthracis Ames "Ancestor". J Bacteriol. 2009 Jan;191(1):445-6. doi: 10.1128/JB.01347-08. Epub 2008 Oct 24. [Article]
  6. 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]
  7. Bourne CR, Wakeham N, Nammalwar B, Tseitin V, Bourne PC, Barrow EW, Mylvaganam S, Ramnarayan K, Bunce RA, Berlin KD, Barrow WW: Structure-activity relationship for enantiomers of potent inhibitors of B. anthracis dihydrofolate reductase. Biochim Biophys Acta. 2013 Jan;1834(1):46-52. doi: 10.1016/j.bbapap.2012.09.001. Epub 2012 Sep 20. [Article]
  8. Johnson SL, Daligault HE, Davenport KW, Jaissle J, Frey KG, Ladner JT, Broomall SM, Bishop-Lilly KA, Bruce DC, Gibbons HS, Coyne SR, Lo CC, Meincke L, Munk AC, Koroleva GI, Rosenzweig CN, Palacios GF, Redden CL, Minogue TD, Chain PS: Complete genome sequences for 35 biothreat assay-relevant bacillus species. Genome Announc. 2015 Apr 30;3(2). pii: e00151-15. doi: 10.1128/genomeA.00151-15. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB082345-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamineexperimentalunknownDetails