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
- Functionsdihydrofolate reductase activity / NADP bindingProcessesglycine 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
- DHFR_1 (PF00186)
- 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
Resource Link UniProtKB ID P16184 UniProtKB Entry Name DYR_PNECA GenBank Protein ID 169408 GenBank Gene ID M26495 - General References
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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 ID Name Drug group Pharmacological action? Actions Details DB02026 Furo[2,3d]Pyrimidine Antifolate experimental unknown Details DB02427 2,4-Diamino-6-[N-(2',5'-Dimethoxybenzyl)-N-Methylamino]Quinazoline experimental unknown Details DB02559 6-(Octahydro-1h-Indol-1-Ylmethyl)Decahydroquinazoline-2,4-Diamine experimental unknown Details DB03461 Nicotinamide adenine dinucleotide phosphate experimental unknown Details DB03987 2,4-Diamino-6-[N-(3',5'-Dimethoxybenzyl)-N-Methylamino]Pyrido[2,3-D]Pyrimidine experimental unknown Details