Pteridine reductase 1

Details

Name
Pteridine reductase 1
Synonyms
  • 1.5.1.33
  • H region methotrexate resistance protein
  • HMTXR
Gene Name
PTR1
Organism
Leishmania major
Amino acid sequence
>lcl|BSEQ0011031|Pteridine reductase 1
MTAPTVPVALVTGAAKRLGRSIAEGLHAEGYAVCLHYHRSAAEANALSATLNARRPNSAI
TVQADLSNVATAPVSGADGSAPVTLFTRCAELVAACYTHWGRCDVLVNNASSFYPTPLLR
NDEDGHEPCVGDREAMETATADLFGSNAIAPYFLIKAFAHRFAGTPAKHRGTNYSIINMV
DAMTNQPLLGYTIYTMAKGALEGLTRSAALELAPLQIRVNGVGPGLSVLVDDMPPAVWEG
HRSKVPLYQRDSSAAEVSDVVIFLCSSKAKYITGTCVKVDGGYSLTRA
Number of residues
288
Molecular Weight
30456.315
Theoretical pI
7.19
GO Classification
Functions
pteridine reductase activity / thymidylate synthase activity
Processes
cellular response to oxidative stress / methylation / pteridine metabolic process / response to methotrexate / tetrahydrobiopterin biosynthetic process
General Function
Thymidylate synthase activity
Specific Function
Exhibits a NADPH-dependent biopterin reductase activity. Has good activity with folate and significant activity with dihydrofolate and dihydrobiopterin, but not with quinonoid dihydrobiopterin. Confers resistance to methotrexate (MTX).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0011032|Pteridine reductase 1 (PTR1)
ATGACTGCTCCGACCGTGCCGGTGGCGTTGGTAACAGGCGCCGCGAAGCGTCTTGGCCGC
AGTATCGCTGAGGGACTCCACGCGGAGGGGTACGCTGTCTGCTTGCACTATCATCGCTCT
GCTGCAGAAGCGAACGCACTATCCGCGACGCTCAACGCAAGGCGACCGAACAGCGCCATC
ACGGTGCAGGCGGATCTGAGCAACGTTGCCACAGCCCCGGTCAGCGGCGCTGATGGCTCT
GCACCTGTTACCCTCTTCACGCGCTGTGCTGAGTTGGTGGCTGCGTGCTACACCCACTGG
GGACGCTGCGACGTGCTAGTGAACAACGCCTCTTCTTTCTACCCCACGCCGCTGCTGAGG
AATGACGAGGATGGACACGAGCCCTGTGTCGGAGATAGAGAGGCAATGGAGACGGCCACC
GCTGACCTCTTCGGCTCCAACGCGATAGCGCCCTACTTCTTGATTAAGGCGTTCGCGCAT
CGCGTCGCGGGCACCCCAGCCAAGCATCGCGGCACCAACTACTCCATCATCAACATGGTC
GACGCCATGACGAACCAGCCTCTTCTCGGGTACACCATATATACCATGGCCAAAGGGGCG
TTGGAGGGGCTGACACGGTCTGCCGCGCTGGAGCTTGCGCCGCTGCAGATTCGAGTGAAC
GGCGTTGGTCCGGGTTTGTCGGTGCTCGTCGATGACATGCCCCCTGCTGTGTGGGAGGGC
CACCGCAGCAAGGTGCCTCTGTACCAGCGCGATTCCTCCGCCGCAGAGGTGAGCGACGTT
GTTATCTTTCTGTGCTCCTCCAAGGCCAAGTACATCACCGGCACCTGTGTCAAAGTGGAT
GGTGGCTACAGCCTTACCCGGGCCTGA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ01782
UniProtKB Entry NamePTR1_LEIMA
GenBank Protein ID13929426
GenBank Gene IDL01699
General References
  1. Callahan HL, Beverley SM: A member of the aldoketo reductase family confers methotrexate resistance in Leishmania. J Biol Chem. 1992 Dec 5;267(34):24165-8. [Article]
  2. Ivens AC, Peacock CS, Worthey EA, Murphy L, Aggarwal G, Berriman M, Sisk E, Rajandream MA, Adlem E, Aert R, Anupama A, Apostolou Z, Attipoe P, Bason N, Bauser C, Beck A, Beverley SM, Bianchettin G, Borzym K, Bothe G, Bruschi CV, Collins M, Cadag E, Ciarloni L, Clayton C, Coulson RM, Cronin A, Cruz AK, Davies RM, De Gaudenzi J, Dobson DE, Duesterhoeft A, Fazelina G, Fosker N, Frasch AC, Fraser A, Fuchs M, Gabel C, Goble A, Goffeau A, Harris D, Hertz-Fowler C, Hilbert H, Horn D, Huang Y, Klages S, Knights A, Kube M, Larke N, Litvin L, Lord A, Louie T, Marra M, Masuy D, Matthews K, Michaeli S, Mottram JC, Muller-Auer S, Munden H, Nelson S, Norbertczak H, Oliver K, O'neil S, Pentony M, Pohl TM, Price C, Purnelle B, Quail MA, Rabbinowitsch E, Reinhardt R, Rieger M, Rinta J, Robben J, Robertson L, Ruiz JC, Rutter S, Saunders D, Schafer M, Schein J, Schwartz DC, Seeger K, Seyler A, Sharp S, Shin H, Sivam D, Squares R, Squares S, Tosato V, Vogt C, Volckaert G, Wambutt R, Warren T, Wedler H, Woodward J, Zhou S, Zimmermann W, Smith DF, Blackwell JM, Stuart KD, Barrell B, Myler PJ: The genome of the kinetoplastid parasite, Leishmania major. Science. 2005 Jul 15;309(5733):436-42. [Article]
  3. Bello AR, Nare B, Freedman D, Hardy L, Beverley SM: PTR1: a reductase mediating salvage of oxidized pteridines and methotrexate resistance in the protozoan parasite Leishmania major. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11442-6. [Article]
  4. Nare B, Hardy LW, Beverley SM: The roles of pteridine reductase 1 and dihydrofolate reductase-thymidylate synthase in pteridine metabolism in the protozoan parasite Leishmania major. J Biol Chem. 1997 May 23;272(21):13883-91. [Article]
  5. Gourley DG, Schuttelkopf AW, Leonard GA, Luba J, Hardy LW, Beverley SM, Hunter WN: Pteridine reductase mechanism correlates pterin metabolism with drug resistance in trypanosomatid parasites. Nat Struct Biol. 2001 Jun;8(6):521-5. [Article]
  6. Luba J, Nare B, Liang PH, Anderson KS, Beverley SM, Hardy LW: Leishmania major pteridine reductase 1 belongs to the short chain dehydrogenase family: stereochemical and kinetic evidence. Biochemistry. 1998 Mar 24;37(12):4093-104. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02338NADPHexperimentalunknownDetails
DB025322,4,6-TriaminoquinazolineexperimentalunknownDetails
DB03461Nicotinamide adenine dinucleotide phosphateexperimentalunknownDetails
DB04400L-erythro-7,8-dihydrobiopterinexperimentalunknownDetails