Target+-+bifunctional+dihydrofolate+reductase-thymidylate+synthase+---------------------------------+Tom


 * Target (protein/gene name):** bifunctional dihydrofolate reductase-thymidylate synthase


 * Protein ID (NP or XP #) or Wolbachia#:** TDR targetID: 3944


 * Organism:** //Plasmodium falciparum//

aused by a parasite that is passed from one human to another by the bite of infected //Anopheles // mosquitoes. After infection, the parasites (called sporozoites) travel through the bloodstream to the liver, where they mature and release another form, the merozoites. The parasites enter the bloodstream and infect red blood cells.
 * Background/Disease Information:** Plasmodium falciprum is commonly known to cause malaria in human. Malaria is

(http://www.ncbi.nlm.nih.gov/pubmed/16549005)
 * Essentiality of this protein:** It is very essential since it avoids the usage of antibiotics and other medications.


 * Complex of enzymes:** not significantly complex


 * EC#:** 1.5.1.3

http://www.brenda-enzymes.org/php/result_flat.php4?ecno=1.5.1.3&Suchword=&organism%5B%5D=Plasmodium+falciparum&show_tm=0
 * Link to BRENDA EC# page:**


 * Enzyme Assay information (spectrophotometric, coupled assay ?, reagents):**It is linked to sigma aldrich website. (http://www.sigmaaldrich.com/etc/medialib/docs/Sigma/Enzyme_Assay/dihydrofolatereductase.Par.0001.File.tmp/dihydrofolatereductase.pdf)
 * Structure Available (PDB or Homology model):**
 * http://www.pdb.org/pdb/explore/explore.do?structureId=1J3I


 * Target :** see the link (http://tdrtargets.org/targets/view?gene_id=3944)


 * Current Inhibitors:** listed below
 * || INHIBITORS || ORGANISM || COMMENTARY || LITERATURE || IMAGE ||
 * (1E)-1-[4-[(3,5-dichloropyridin-4-yl)oxy]phenyl]ethanone thiosemicarbazone ||  || - || 703329 ||   ||
 * 1,1'-{6-[(4-nitrophenyl)amino]-1,3,5-triazine-2,4-diyl}bis(4-benzylpyrazinediium) ||  || minimal inhibitory concentration: 0.003536 mM || 711727 ||   ||
 * 1,1'-{6-[(4-nitrophenyl)amino]-1,3,5-triazine-2,4-diyl}bis(4-methylpyrazinediium) ||  || minimal inhibitory concentration: 0.002418 mM || 711727 ||   ||
 * 1,1'-{6-[(4-nitrophenyl)amino]-1,3,5-triazine-2,4-diyl}bis(4-phenylpyrazinediium) ||  || minimal inhibitory concentration: 0.018 mM || 711727 ||   ||
 * 1-(4-chlorophenyl)-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine ||  || - || 703329 ||   ||
 * 1-[3-(3,4-dichlorophenoxy)propyloxy]-5-isopropylbiguanide ||  || i.e. PS-16 || 703329 || - ||
 * 1-[3-(4-chlorophenoxy)propyloxy]-5-isopropylbiguanide ||  || i.e. PS-33 || 703329 || - ||
 * 2,2'-({6-[(4-nitrophenyl)amino]-1,3,5-triazine-2,4-diyl}diimino)diethanol ||  || minimal inhibitory concentration: 0.149 mM || 711727 ||   ||
 * 2,3-bis(hydrazino)quinoxaline ||  || - || 703329 ||   ||   ||


 * Expression Information:** upregulation ranking shows that this gene ranks in the mid 40-60% group of genes (In a form of early schizont and late trophozoite). Also, expression system is Escherichia coli bl21(de3).


 * Purification Method:**


 * Image of protein (PyMol or etc):**
 * [[image:vdsstream/1j3i_bio_r_500.jpg]] ||
 * P. falciparum dihydrofolate reductase-thymidylate synthase (DOI: 10.2210, UniProtKB: P13922).

http://www.pdb.org/pdb/explore/explore.do?structureId=1J3I ||
 * -Amino acid sequence:**


 * length of your protein in Amino Acids =**


 * Molecular Weight of your protein in kiloDaltons using the [|Expasy ProtParam]website =**

//Arabidopsis thaliana// [|NP_195183] THY-2 (thymidylate synthase 2); dihydrofolate reductase/ th... | [|OrthoMCL] //Arabidopsis thaliana// [|NP_179230] THY-1 (THYMIDYLATE SYNTHASE 1); dihydrofolate reductase/ th... | [|OrthoMCL] //Babesia bovis// [|3I3R] B Chain B, X-Ray Structure Dihydrofolate ReductaseTHYMIDYLA... | [|OrthoMCL] //Babesia bovis// [|XP_001609606.1] dihydrofolate reductase/thymidilate synthase ... | [|OrthoMCL] //Brugia malayi// [|Bm1_33465] thymidylate synthase, putative... | [|OrthoMCL] //Caenorhabditis elegans// [|Y110A7A.4] CE24124 WBGene00022455 thymidylate synthase status:Confirmed... | [|OrthoMCL] //Cryptosporidium hominis// [|Chro.40506] chain A, crystal structure of Dhfr ... | [|OrthoMCL] //Cryptosporidium muris// [|CMU_010300] thymidylate synthase family protein ... | [|OrthoMCL] //Cryptosporidium neoformas// [|XP_567501] thymidylate synthase ... | [|OrthoMCL] //Cryptosporidium parvum// [|cgd4_4460] dihydrofolate reductase-thymidylate synthase ... | [|OrthoMCL]
 * Orthologs:** Numerous but first 10 are:

- By orthology to known druggable target = - By sequence similar to non ortholog = (website: http://tdrtargets.org/targets/view?gene_id=3944)
 * - Druggability:** druggability index: 1 (0 to 1 range)
 * ~ **Species** ||~ **Known druggable target** ||~ **Reference** ||~ **Linked compounds** ||
 * Homo sapiens || [|Thymidylate synthase] || [|Show papers] || [|show compounds] ||
 * Plasmodium falciparum K1/Thailand || [|Dihydrofolate reductase] || [|Show papers] || [|show compounds] ||
 * Mus musculus || [|Thymidylate synthase] || [|Show papers] || [|show compounds] ||
 * Leishmania major || [|Dihydrofolate reductase] || [|Show papers] || [|show compounds] ||
 * Plasmodium berghei strain ANKA || [|Dihydrofolate reductase] || [|Show papers] || [|show compounds] ||
 * Toxoplasma gondii || [|Dihydrofolate reductase] || [|Show papers] || [|show compounds] ||
 * Escherichia coli || [|Thymidylate synthase] || [|Show papers] || [|show compounds] ||
 * Rattus norvegicus || [|Thymidylate synthase] || [|Show papers] || [|show compounds] ||
 * Lactobacillus casei || [|Thymidylate synthase] || [|Show papers] || [|show compounds] ||
 * Cryptosporidium hominis TU502 || [|Dihydrofolate reductase] || [|Show papers] || [|show compounds] ||
 * Filobasidiella neoformans || [|Thymidylate synthase] || [|Show papers] || [|show compounds] ||
 * ~ Species ||~ Target ||~ Length ||~ Source ||~ Identity ||~ Alignment span ||~ Reference ||~ Linked compounds ||
 * Gallus gallus || [|Dihydrofolate reductase] || 189 aa || [| P00378] || 28.9% || 201 aa || [|Show papers] || [|show compounds] ||
 * Rattus norvegicus || [|Dihydrofolate reductase] || 187 aa || [| NP_569084.1] || 29.8% || 205 aa || [|Show papers] || [|show compounds] ||
 * Mus musculus || [|Dihydrofolate reductase] || 186 aa || [| P00375] || 30.7% || 205 aa || [|Show papers] || [|show compounds] ||
 * Pneumocystis jirovecii || [|Dihydrofolate reductase] || 206 aa || [| Q9UUP5] || 32.7% || 168 aa || [|Show papers] || [|show compounds] ||
 * Candida albicans || [|Dihydrofolate reductase] || 192 aa || [| P22906] || 30.2% || 162 aa || [|Show papers] || [|show compounds] ||
 * Homo sapiens || [|Dihydrofolate reductase] || 186 aa || [| P00374] || 29.7% || 202 aa || [|Show papers] || [|show compounds] ||
 * Pneumocystis carinii || [|Dihydrofolate reductase] || 206 aa || [| P16184] || 30.0% || 170 aa || [|Show papers] || [|show compounds] ||


 * - Additional Info.:** Ki: 0.03 nM, IC50: 1820.0 nM


 * (TDR info:** http://tdrtargets.org/targets/view?gene_id=3944)