ID DRTS_PLAVI Reviewed; 623 AA. AC O02604; O15873; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2000, sequence version 2. DT 16-JUN-2009, entry version 60. DE RecName: Full=Bifunctional dihydrofolate reductase-thymidylate synthase; DE Short=DHFR-TS; DE Includes: DE RecName: Full=Dihydrofolate reductase; DE EC=1.5.1.3; DE Includes: DE RecName: Full=Thymidylate synthase; DE EC=2.1.1.45; OS Plasmodium vivax. OC Eukaryota; Alveolata; Apicomplexa; Aconoidasida; Haemosporida; OC Plasmodium; Plasmodium (Plasmodium). OX NCBI_TaxID=5855; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=Isolate Ari/Pakistan, Isolate BUR-151, and Isolate BUR-98; RX MEDLINE=98241515; PubMed=9573357; DOI=10.1016/S0378-1119(98)00118-8; RA Eldin de Pecoulas P., Basco L.K., Tahar R., Ouatas T., Mazabraud A.; RT "Analysis of the Plasmodium vivax dihydrofolate reductase-thymidylate RT synthase gene sequence."; RL Gene 211:177-185(1998). CC -!- CATALYTIC ACTIVITY: 5,6,7,8-tetrahydrofolate + NADP(+) = 7,8- CC dihydrofolate + NADPH. CC -!- CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + dUMP = CC dihydrofolate + dTMP. CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; CC tetrahydrofolate from dihydrofolate: step 1/1. CC -!- DOMAIN: The repeat region is missing in the pyrimethamine- CC resistant isolates BUR-98 and BUR-151. CC -!- MISCELLANEOUS: The reaction catalyzed by this enzyme represents an CC essential step for de novo glycine and purine synthesis, DNA CC precursor synthesis, and for the conversion of dUMP to dTMP. CC -!- SIMILARITY: In the N-terminal section; belongs to the CC dihydrofolate reductase family. CC -!- SIMILARITY: In the C-terminal section; belongs to the thymidylate CC synthase family. CC -!- SIMILARITY: Contains 1 DHFR (dihydrofolate reductase) domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X98123; CAA66805.1; -; Genomic_DNA. DR PIR; JC6568; JC6568. DR PDB; 2BL9; X-ray; 1.90 A; A=1-238. DR PDB; 2BLA; X-ray; 2.50 A; A=1-238. DR PDB; 2BLB; X-ray; 3.00 A; A=1-238. DR PDB; 2BLC; X-ray; 2.25 A; A=1-238. DR PDBsum; 2BL9; -. DR PDBsum; 2BLA; -. DR PDBsum; 2BLB; -. DR PDBsum; 2BLC; -. DR SMR; O02604; 338-623. DR BRENDA; 1.5.1.3; 257191. DR BRENDA; 2.1.1.45; 257191. DR GO; GO:0004146; F:dihydrofolate reductase activity; IEA:EC. DR GO; GO:0004799; F:thymidylate synthase activity; IEA:EC. DR GO; GO:0006231; P:dTMP biosynthetic process; IEA:InterPro. DR GO; GO:0006545; P:glycine biosynthetic process; IEA:InterPro. DR GO; GO:0006730; P:one-carbon compound metabolic process; IEA:UniProtKB-KW. DR GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW. DR InterPro; IPR012262; DHFR-TS. DR InterPro; IPR001796; DHFR_reg. DR InterPro; IPR017925; Dihydrofolate_reductase_CS. DR InterPro; IPR000398; Thymidylat_synth_C. DR Gene3D; G3DSA:3.30.572.10; Thymidylat_synth_C; 1. DR PANTHER; PTHR11549:SF2; Thymidylat_synth_C; 1. DR Pfam; PF00186; DHFR_1; 1. DR Pfam; PF00303; Thymidylat_synt; 1. DR PIRSF; PIRSF000389; DHFR-TS; 1. DR PRINTS; PR00108; THYMDSNTHASE. DR ProDom; PD001180; Thymidylat_synth; 1. DR TIGRFAMs; TIGR03284; thym_sym; 1. DR PROSITE; PS00075; DHFR_1; 1. DR PROSITE; PS51330; DHFR_2; 1. DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1. PE 1: Evidence at protein level; KW 3D-structure; Methyltransferase; Multifunctional enzyme; NADP; KW Nucleotide biosynthesis; One-carbon metabolism; Oxidoreductase; KW Repeat; Transferase. FT CHAIN 1 623 Bifunctional dihydrofolate reductase- FT thymidylate synthase. FT /FTId=PRO_0000186351. FT DOMAIN 9 237 DHFR. FT REPEAT 88 91 1. FT REPEAT 94 97 2. FT REPEAT 100 103 3. FT REGION 88 103 3 X 4 AA repeats of G-G-D-N. FT REGION 337 623 Thymidylate synthase. FT ACT_SITE 505 505 By similarity. FT VARIANT 58 58 S -> R (in the pyrimethamine-resistant FT isolates BUR-98 and BUR-151). FT VARIANT 117 117 S -> N (in the pyrimethamine-resistant FT isolates BUR-98 and BUR-151). FT HELIX 4 7 FT STRAND 10 19 FT STRAND 23 26 FT STRAND 38 41 FT STRAND 46 48 FT HELIX 51 62 FT HELIX 66 68 FT HELIX 69 83 FT STRAND 109 114 FT HELIX 115 119 FT HELIX 123 125 FT STRAND 131 136 FT TURN 142 144 FT STRAND 150 153 FT HELIX 155 163 FT STRAND 170 174 FT HELIX 176 184 FT STRAND 189 200 FT STRAND 203 205 FT HELIX 211 213 FT STRAND 214 219 FT STRAND 223 225 FT STRAND 228 237 SQ SEQUENCE 623 AA; 71057 MW; 3E6E958F04FB5828 CRC64; MEDLSDVFDI YAICACCKVA PTSEGTKNEP FSPRTFRGLG NKGTLPWKCN SVDMKYFSSV TTYVDESKYE KLKWKRERYL RMEASQGGGD NTSGGDNTHG GDNADKLQNV VVMGRSSWES IPKQYKPLPN RINVVLSKTL TKEDVKEKVF IIDSIDDLLL LLKKLKYYKC FIIGGAQVYR ECLSRNLIKQ IYFTRINGAY PCDVFFPEFD ESQFRVTSVS EVYNSKGTTL DFLVYSKVGG GVDGGASNGS TATALRRTAM RSTAMRRNVA PRTAAPPMGP HSRANGERAP PRARARRTTP RQRKTTSCTS ALTTKWGRKT RSTCKILKFT TASRLMQHPE YQYLGIIYDI IMNGNKQGDR TGVGVMSNFG YMMKFNLSEY FPLLTTKKLF LRGIIEELLW FIRGETNGNT LLNKNVRIWE ANGTREFLDN RKLFHREVND LGPIYGFQWR HFGAEYTNMH DNYEDKGVDQ LKNVIHLIKN EPTSRRIILC AWNVKDLDQM ALPPCHILCQ FYVFDGKLSC IMYQRSCDLG LGVPFNIASY SIFTHMIAQV CNLQPAQFIH ILGNAHVYNN HVDSLKVQLN RIPYPFPTLK LNPEVKNIED FTISDFTIEN YVHHDKITME MAA //