Dihydrofolate reductase

Details

Name
Dihydrofolate reductase
Synonyms
  • 1.5.1.3
Gene Name
Not Available
Organism
Pneumocystis carinii
Amino acid sequence
>lcl|BSEQ0011101|Dihydrofolate reductase
MNQQKSLTLIVALTTSYGIGRSNSLPWKLKKEISYFKRVTSFVPTFDSFESMNVVLMGRK
TWESIPLQFRPLKGRINVVITRNESLDLGNGIHSAKSLDHALELLYRTYGSESSVQINRI
FVIGGAQLYKAAMDHPKLDRIMATIIYKDIHCDVFFPLKFRDKEWSSVWKKEKHSDLESW
VGTKVPHGKINEDGFDYEFEMWTRDL
Number of residues
206
Molecular Weight
23883.325
Theoretical pI
9.67
GO Classification
Functions
dihydrofolate reductase activity / 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|BSEQ0003086|621 bp
ATGAATCAGCAAAAGTCTTTAACATTGATTGTTGCACTTACAACTTCTTATGGAATTGGC
CGATCAAACTCTCTTCCATGGAAATTAAAGAAAGAAATAAGTTATTTTAAACGAGTAACC
TCTTTTGTACCAACTTTTGATTCATTTGAATCGATGAATGTTGTATTGATGGGTCGAAAA
ACATGGGAAAGTATTCCTTTGCAATTTCGGCCCCTTAAAGGTCGTATTAATGTTGTTATC
ACTCGAAATGAATCTCTGGATCTAGGAAATGGAATTCATTCTGCAAAATCCTTGGATCAT
GCTTTGGAATTGTTATATCGTACATATGGTTCTGAAAGTTCGGTTCAAATTAATCGAATT
TTCGTTATAGGTGGTGCACAGCTATATAAAGCAGCTATGGATCATCCTAAATTAGATAGA
ATTATGGCTACAATAATATACAAGGATATTCATTGTGATGTATTTTTTCCACTTAAATTT
AGGGATAAAGAATGGTCTTCTGTATGGAAAAAAGAAAAACATTCAGATTTAGAATCTTGG
GTTGGTACTAAAGTTCCTCATGGTAAAATAAATGAAGACGGTTTTGATTATGAATTCGAA
ATGTGGACAAGAGATTTATAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP16184
UniProtKB Entry NameDYR_PNECA
GenBank Protein ID169408
GenBank Gene IDM26495
General References
  1. Edman JC, Edman U, Cao M, Lundgren B, Kovacs JA, Santi DV: Isolation and expression of the Pneumocystis carinii dihydrofolate reductase gene. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8625-9. [Article]
  2. Champness JN, Achari A, Ballantine SP, Bryant PK, Delves CJ, Stammers DK: The structure of Pneumocystis carinii dihydrofolate reductase to 1.9 A resolution. Structure. 1994 Oct 15;2(10):915-24. [Article]
  3. Cody V, Galitsky N, Rak D, Luft JR, Pangborn W, Queener SF: Ligand-induced conformational changes in the crystal structures of Pneumocystis carinii dihydrofolate reductase complexes with folate and NADP+. Biochemistry. 1999 Apr 6;38(14):4303-12. [Article]
  4. Cody V, Chan D, Galitsky N, Rak D, Luft JR, Pangborn W, Queener SF, Laughton CA, Stevens MF: Structural studies on bioactive compounds. 30. Crystal structure and molecular modeling studies on the Pneumocystis carinii dihydrofolate reductase cofactor complex with TAB, a highly selective antifolate. Biochemistry. 2000 Apr 4;39(13):3556-64. [Article]
  5. Cody V, Galitsky N, Luft JR, Pangborn W, Rosowsky A, Queener SF: Structure-based enzyme inhibitor design: modeling studies and crystal structure analysis of Pneumocystis carinii dihydrofolate reductase ternary complex with PT653 and NADPH. Acta Crystallogr D Biol Crystallogr. 2002 Jun;58(Pt 6 Pt 2):946-54. Epub 2002 May 29. [Article]
  6. Cody V, Galitsky N, Luft JR, Pangborn W, Queener SF, Gangjee A: Analysis of quinazoline and pyrido[2,3-d]pyrimidine N9-C10 reversed-bridge antifolates in complex with NADP+ and Pneumocystis carinii dihydrofolate reductase. Acta Crystallogr D Biol Crystallogr. 2002 Sep;58(Pt 9):1393-9. Epub 2002 Aug 23. [Article]
  7. Cody V, Luft JR, Pangborn W, Gangjee A, Queener SF: Structure determination of tetrahydroquinazoline antifolates in complex with human and Pneumocystis carinii dihydrofolate reductase: correlations between enzyme selectivity and stereochemistry. Acta Crystallogr D Biol Crystallogr. 2004 Apr;60(Pt 4):646-55. Epub 2004 Mar 23. [Article]
  8. Cody V, Pace J, Chisum K, Rosowsky A: New insights into DHFR interactions: analysis of Pneumocystis carinii and mouse DHFR complexes with NADPH and two highly potent 5-(omega-carboxy(alkyloxy) trimethoprim derivatives reveals conformational correlations with activity and novel parallel ring stacking interactions. Proteins. 2006 Dec 1;65(4):959-69. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02026Furo[2,3d]Pyrimidine AntifolateexperimentalunknownDetails
DB024272,4-Diamino-6-[N-(2',5'-Dimethoxybenzyl)-N-Methylamino]QuinazolineexperimentalunknownDetails
DB025596-(Octahydro-1h-Indol-1-Ylmethyl)Decahydroquinazoline-2,4-DiamineexperimentalunknownDetails
DB03461Nicotinamide adenine dinucleotide phosphateexperimentalunknownDetails
DB039872,4-Diamino-6-[N-(3',5'-Dimethoxybenzyl)-N-Methylamino]Pyrido[2,3-D]PyrimidineexperimentalunknownDetails