Target+- dihydrofolate+reductase-thymidylate+synthase+(T.+cruzi)

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dihydrofolate reductase-thymidylate synthase Tc00.1047053509153.90 3547029 XP_815327.1 Trypanosoma cruzi strain CL Brener Risk Group 2 (RG2) - Parasitic Agents Chagas disease is a tropical parasitic disease caused by the flagellate protozoan Trypanosoma cruzi. T. cruzi is commonly transmitted to humans and other mammals by an insect vector, the blood-sucking "kissing bugs" of the subfamily Triatominae (family Reduviidae) most commonly species belonging to the Triatoma, Rhodnius, and Panstrongylus genera. The disease may also be spread through blood transfusion and organ transplantation, ingestion of food contaminated with parasites, and from a mother to her fetus. The symptoms of Chagas disease vary over the course of an infection. In the early, acute stage, symptoms are mild and usually produce no more than local swelling at the site of infection. The initial acute phase is responsive to antiparasitic treatments, with 60–90% cure rates. After 4–8 weeks, individuals with active infections enter the chronic phase of Chagas disease that is asymptomatic for 60–80% of chronically infected individuals through their lifetime. The antiparasitic treatments also appear to delay or prevent the development of disease symptoms during the chronic phase of the disease, but 20–40% of chronically infected individuals will still eventually develop life-threatening heart and digestive system disorders. The currently available antiparasitic treatments for Chagas disease are benznidazole and nifurtimox, which can cause temporary side effects in many patients including skin disorders, brain toxicity, and digestive system irritation. Chagas disease is contracted primarily in the Americas, particularly in poor, rural areas of Mexico, Central America, and South America; very rarely, the disease has originated in the Southern United States. The insects that spread the disease are known by various local names, including vinchuca in Argentina, Bolivia, Chile and Paraguay, barbeiro (the barber) in Brazil, pito in Colombia, chinche in Central America, chipo in Venezuela, chupança, chinchorro, and "the kissing bug". It is estimated that as many as 8 to 11 million people in Mexico, Central America, and South America have Chagas disease, most of whom do not know they are infected. Large-scale population movements from rural to urban areas of Latin America and to other regions of the world have increased the geographic distribution of Chagas disease, and cases have been noted in many countries, particularly in Europe. Control strategies have mostly focused on eliminating the triatomine insect vector and preventing transmission from other sources. --Wikipedia significant loss of fitness in bloodstream forms (6 days) in a study on African trypanosome [alsford] No 1.5.1.3 & 2.1.1.45 [] [] DHFR [|reaction diagram] [|dihydrofolate] [|NADPH] TS [|reaction diagram] [|5,10-methylenetetrahydrofolate] [|dUMP] Assay for Dihydrofolate Reductase (1.5.1.3). [] An enzyme with this EC number or name (thymidylate synthase) or sequence has been assayed in Trypanosoma cruzi. [] 3INV (direct match) 0.8 this [|paper] reports potential inhibitors with IC 50 values in the nanomolar range, the best around 20-30 nM. the inhibitors synthesized for the paper were also active for human DHFR, and modifications were not effective in biasing the inhibition towards the parasite. also refer to this [|paper]. Escherichia coli Bl21(de3) Plyss Plasmid pET11c N/A [] >gi|71653378|ref|XP_815327.1| dihydrofolate reductase-thymidylate synthase [Trypanosoma cruzi strain CL Brener] MSLFKIRMPETVAEGTRLALRAFSLVVAVDEHGGIGDGRSIPWNVPEDMKFFRDLTTKLRGKNVKPSPAK RNAVVMGRKTWDSIPPKFRPLPGRLNVVLSSTLTTQHLLDGLPDEEKRNLHADSIVAVNGGLEQALRLLA SPNYTPSIETVYCIGGGSVYAEALRPPCVHLLQAIYRTTIRASESSCSVFFRVPESGTEAAAGIEWQRET ISEELTSANGNETKYYFEKLIPRNREEEQYLSLVDRIIREGNVKHDRTGVGTLSIFGAQMRFSLRNNRLP LLTTKRVFWRGVCEELLWFLRGETYAKKLSDKGVHIWDDNGSRAFLDSRGLTEYEEMDLGPVYGFQWRHF GAAYTHHDANYDGQGVDQIKAIVETLKTNPDDRRMLFTAWNPSALPRMALPPCHLLAQFYVSNGELSCML YQRSCDMGLGVPFNIASYALLTILIAKATGLRPGELVHTLGDAHVYSNHVEPCNEQLKRVPRAFPYLVFR REREFLEDYEEGDMEVIDYAPYPPISMKMAV 521 58853.2 Da 73800 (reduced cysteines) >gi|164451099:234741-236306 Trypanosoma cruzi strain CL Brener 1047053517157 genomic scaffold, whole genome shotgun sequence ATGTCGCTGTTTAAGATCCGCATGCCGGAGACGGTGGCGGAGGGGACACGTCTCGCACTGCGTGCCTTTT CCCTCGTTGTAGCGGTCGACGAGCACGGCGGCATTGGGGACGGGCGGTCGATCCCATGGAATGTGCCCGA GGACATGAAGTTTTTCCGGGATTTGACAACAAAACTGCGGGGGAAGAACGTCAAACCATCGCCTGCGAAG CGCAACGCCGTTGTGATGGGCCGCAAGACGTGGGACAGCATTCCGCCCAAATTCCGCCCGCTTCCCGGTC GCCTGAACGTCGTTTTGTCGTCCACCCTCACGACGCAACACCTCTTGGACGGCCTGCCAGACGAAGAAAA ACGGAATTTGCATGCCGACAGCATTGTGGCGGTAAATGGTGGACTCGAGCAGGCATTGCGGTTGCTCGCG <span style="font-family: 'Lucida Console',Monaco,monospace;">TCCCCCAATTACACGCCGAGCATTGAGACGGTCTACTGCATTGGTGGCGGCTCTGTGTATGCGGAGGCCC <span style="font-family: 'Lucida Console',Monaco,monospace;">TTCGCCCGCCGTGCGTTCATTTGCTGCAAGCCATTTACCGCACCACCATCCGCGCCAGCGAGTCTTCTTG <span style="font-family: 'Lucida Console',Monaco,monospace;">CAGCGTGTTTTTTCGCGTTCCCGAGTCGGGTACGGAGGCGGCGGCGGGGATTGAGTGGCAGCGGGAGACA <span style="font-family: 'Lucida Console',Monaco,monospace;">ATCTCCGAGGAGCTCACGTCGGCAAACGGCAACGAGACAAAGTACTACTTTGAGAAGCTCATCCCACGCA <span style="font-family: 'Lucida Console',Monaco,monospace;">ACAGAGAGGAGGAGCAGTATCTAAGCCTTGTGGATCGCATCATACGCGAGGGGAATGTGAAGCATGACCG <span style="font-family: 'Lucida Console',Monaco,monospace;">CACTGGGGTGGGCACGCTCTCCATCTTTGGCGCACAGATGCGTTTCTCGCTCCGCAACAATCGCCTACCA <span style="font-family: 'Lucida Console',Monaco,monospace;">CTTTTGACAACGAAGCGGGTTTTTTGGCGCGGTGTGTGCGAGGAACTGCTGTGGTTTCTACGGGGCGAAA <span style="font-family: 'Lucida Console',Monaco,monospace;">CATATGCCAAAAAGTTAAGTGACAAGGGAGTCCACATATGGGACGACAACGGCTCGCGCGCGTTTCTTGA <span style="font-family: 'Lucida Console',Monaco,monospace;">CAGTCGTGGCCTCACAGAGTACGAGGAGATGGACCTCGGTCCTGTCTACGGCTTTCAGTGGCGTCACTTT <span style="font-family: 'Lucida Console',Monaco,monospace;">GGTGCCGCCTACACACACCATGATGCCAACTATGACGGACAGGGTGTGGATCAAATCAAGGCAATCGTTG <span style="font-family: 'Lucida Console',Monaco,monospace;">AAACGCTAAAGACAAATCCTGACGATCGCCGGATGCTATTCACGGCATGGAATCCGAGCGCTTTGCCCAG <span style="font-family: 'Lucida Console',Monaco,monospace;">GATGGCCCTACCACCGTGCCACCTGCTCGCACAGTTTTACGTGAGCAATGGGGAACTGTCTTGCATGCTC <span style="font-family: 'Lucida Console',Monaco,monospace;">TACCAGCGCTCATGTGACATGGGCCTTGGCGTCCCGTTCAACATTGCCTCCTACGCCCTCTTGACCATCC <span style="font-family: 'Lucida Console',Monaco,monospace;">TCATCGCAAAGGCGACGGGGCTGCGGCCGGGAGAGTTGGTGCACACCCTTGGTGACGCTCACGTGTACAG <span style="font-family: 'Lucida Console',Monaco,monospace;">CAATCACGTCGAGCCGTGCAATGAGCAACTGAAACGTGTGCCACGTGCCTTTCCGTATCTTGTGTTTCGC <span style="font-family: 'Lucida Console',Monaco,monospace;">CGCGAGCGCGAGTTCCTGGAGGACTACGAGGAGGGTGACATGGAGGTCATTGACTATGCGCCATACCCTC <span style="font-family: 'Lucida Console',Monaco,monospace;">CCATCTCCATGAAGATGGCGGTTTAG 57.54% <span style="font-family: 'Lucida Console',Monaco,monospace;">ATGTCCCTGTTCAAAATCCGTATGCCTGAGACTGTGGCAGAAGGCACCCGCCTGGCGCTC <span style="font-family: 'Lucida Console',Monaco,monospace;">CGTGCGTTTTCTCTCGTTGTGGCCGTTGATGAGCACGGTGGTATCGGTGATGGCCGCTCC <span style="font-family: 'Lucida Console',Monaco,monospace;">ATCCCTTGGAACGTACCGGAGGACATGAAATTCTTCCGTGACCTGACGACCAAACTCCGT <span style="font-family: 'Lucida Console',Monaco,monospace;">GGTAAAAACGTTAAACCATCTCCGGCGAAGCGTAACGCAGTTGTTATGGGTCGTAAAACC <span style="font-family: 'Lucida Console',Monaco,monospace;">TGGGATTCTATCCCGCCGAAATTCCGTCCTCTGCCAGGCCGCCTGAATGTTGTTCTGTCC <span style="font-family: 'Lucida Console',Monaco,monospace;">TCTACTCTGACCACCCAGCATCTCCTCGACGGTCTCCCGGATGAAGAGAAACGTAACCTG <span style="font-family: 'Lucida Console',Monaco,monospace;">CACGCGGACTCTATCGTTGCGGTTAACGGCGGTCTGGAACAGGCCCTGCGCCTGCTCGCC <span style="font-family: 'Lucida Console',Monaco,monospace;">TCTCCAAACTATACCCCGTCTATCGAAACTGTGTACTGCATCGGCGGTGGTTCTGTTTAT <span style="font-family: 'Lucida Console',Monaco,monospace;">GCTGAAGCGCTGCGTCCGCCATGCGTTCATCTGCTGCAGGCGATCTACCGTACCACCATC <span style="font-family: 'Lucida Console',Monaco,monospace;">CGTGCCTCTGAGTCTAGCTGTAGCGTGTTCTTTCGTGTCCCGGAATCTGGTACCGAAGCT <span style="font-family: 'Lucida Console',Monaco,monospace;">GCCGCAGGTATCGAATGGCAGCGTGAGACTATTTCCGAGGAACTGACCTCTGCGAACGGT <span style="font-family: 'Lucida Console',Monaco,monospace;">AACGAAACCAAATACTACTTCGAAAAACTGATCCCGCGCAACCGTGAGGAAGAACAATAC <span style="font-family: 'Lucida Console',Monaco,monospace;">CTGTCTCTGGTTGACCGTATCATTCGTGAAGGTAACGTCAAACATGACCGCACTGGTGTT <span style="font-family: 'Lucida Console',Monaco,monospace;">GGTACCCTCTCTATTTTCGGTGCGCAGATGCGCTTCTCTCTCCGTAATAACCGCCTGCCA <span style="font-family: 'Lucida Console',Monaco,monospace;">CTGCTCACCACCAAACGTGTTTTCTGGCGTGGTGTTTGCGAAGAACTGCTGTGGTTCCTG <span style="font-family: 'Lucida Console',Monaco,monospace;">CGTGGCGAAACCTACGCGAAAAAACTCTCTGACAAAGGTGTCCACATCTGGGACGACAAC <span style="font-family: 'Lucida Console',Monaco,monospace;">GGTTCTCGCGCGTTCCTGGACAGCCGTGGCCTGACCGAATACGAAGAAATGGACCTGGGT <span style="font-family: 'Lucida Console',Monaco,monospace;">CCTGTTTACGGCTTTCAGTGGCGTCACTTTGGTGCTGCGTACACCCACCACGACGCGAAC <span style="font-family: 'Lucida Console',Monaco,monospace;">TACGACGGCCAAGGTGTTGACCAGATCAAAGCGATCGTTGAAACCCTGAAAACGAATCCA <span style="font-family: 'Lucida Console',Monaco,monospace;">GATGATCGTCGTATGCTGTTCACTGCTTGGAATCCGTCTGCCCTGCCGCGTATGGCTCTC <span style="font-family: 'Lucida Console',Monaco,monospace;">CCTCCTTGCCACCTGCTGGCGCAATTCTACGTGTCTAACGGTGAGCTGTCTTGCATGCTG <span style="font-family: 'Lucida Console',Monaco,monospace;">TACCAGCGTAGCTGCGACATGGGTCTGGGTGTTCCATTCAACATCGCTTCTTACGCCCTC <span style="font-family: 'Lucida Console',Monaco,monospace;">CTGACCATCCTGATCGCGAAAGCGACCGGCCTCCGCCCAGGTGAACTGGTTCATACCCTG <span style="font-family: 'Lucida Console',Monaco,monospace;">GGTGACGCGCACGTTTACTCTAACCACGTTGAACCGTGCAACGAACAACTCAAACGCGTA <span style="font-family: 'Lucida Console',Monaco,monospace;">CCTCGTGCCTTTCCGTACCTGGTTTTCCGTCGTGAACGTGAATTTCTGGAAGACTATGAA <span style="font-family: 'Lucida Console',Monaco,monospace;">GAAGGTGACATGGAAGTTATCGACTATGCGCCGTACCCACCTATCTCTATGAAAATGGCG <span style="font-family: 'Lucida Console',Monaco,monospace;">GTTTAA 54.15% <span style="font-family: 'Lucida Console',Monaco,monospace;">1 ATGTCCCTGTTCAAAATCCGTATGCCTGAGACTGTGGCAGAAGGCACCCGCCT 53 <span style="font-family: 'Lucida Console',Monaco,monospace;">2 CGTGCTCATCAACGGCCACAACGAGAGAAAACGCACGGAGCGCCAGGCGGGTGCCTTCTG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">3 GGCCGTTGATGAGCACGGTGGTATCGGTGATGGCCGCTCCATCCCTTGGAACGTACCGGA 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">4 CCACGGAGTTTGGTCGTCAGGTCACGGAAGAATTTCATGTCCTCCGGTACGTTCCAAGGG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">5 GACGACCAAACTCCGTGGTAAAAACGTTAAACCATCTCCGGCGAAGCGTAACGCAGTTGT 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">6 GGAATTTCGGCGGGATAGAATCCCAGGTTTTACGACCCATAACAACTGCGTTACGCTTCG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">7 ATTCTATCCCGCCGAAATTCCGTCCTCTGCCAGGCCGCCTGAATGTTGTTCTGTCCTCTA 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">8 TCCGGGAGACCGTCGAGGAGATGCTGGGTGGTCAGAGTAGAGGACAGAACAACATTCAGG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">9 TCGACGGTCTCCCGGATGAAGAGAAACGTAACCTGCACGCGGACTCTATCGTTGCGGTTA 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">10 GGAGAGGCGAGCAGGCGCAGGGCCTGTTCCAGACCGCCGTTAACCGCAACGATAGAGTCC 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">11 GCCTGCTCGCCTCTCCAAACTATACCCCGTCTATCGAAACTGTGTACTGCATCGGCGGTG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">12 AGATGAACGCATGGCGGACGCAGCGCTTCAGCATAAACAGAACCACCGCCGATGCAGTAC 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">13 CCGCCATGCGTTCATCTGCTGCAGGCGATCTACCGTACCACCATCCGTGCCTCTGAGTCT 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">14 TCGGTACCAGATTCCGGGACACGAAAGAACACGCTACAGCTAGACTCAGAGGCACGGATG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">15 CCCGGAATCTGGTACCGAAGCTGCCGCAGGTATCGAATGGCAGCGTGAGACTATTTCCGA 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">16 GTAGTATTTGGTTTCGTTACCGTTCGCAGAGGTCAGTTCCTCGGAAATAGTCTCACGCTG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">17 ACGGTAACGAAACCAAATACTACTTCGAAAAACTGATCCCGCGCAACCGTGAGGAAGAAC 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">18 GTTACCTTCACGAATGATACGGTCAACCAGAGACAGGTATTGTTCTTCCTCACGGTTGCG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">19 CCGTATCATTCGTGAAGGTAACGTCAAACATGACCGCACTGGTGTTGGTACCCTCTCTAT 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">20 CGGTTATTACGGAGAGAGAAGCGCATCTGCGCACCGAAAATAGAGAGGGTACCAACACCA 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">21 GCTTCTCTCTCCGTAATAACCGCCTGCCACTGCTCACCACCAAACGTGTTTTCTGGCGTG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">22 GTTTCGCCACGCAGGAACCACAGCAGTTCTTCGCAAACACCACGCCAGAAAACACGTTTG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">23 TTCCTGCGTGGCGAAACCTACGCGAAAAAACTCTCTGACAAAGGTGTCCACATCTGGGAC 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">24 GTCAGGCCACGGCTGTCCAGGAACGCGCGAGAACCGTTGTCGTCCCAGATGTGGACACCT 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">25 ACAGCCGTGGCCTGACCGAATACGAAGAAATGGACCTGGGTCCTGTTTACGGCTTTCAGT 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">26 TCGCGTCGTGGTGGGTGTACGCAGCACCAAAGTGACGCCACTGAAAGCCGTAAACAGGAC 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">27 CCCACCACGACGCGAACTACGACGGCCAAGGTGTTGACCAGATCAAAGCGATCGTTGAAA 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">28 GAACAGCATACGACGATCATCTGGATTCGTTTTCAGGGTTTCAACGATCGCTTTGATCTG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">29 GATGATCGTCGTATGCTGTTCACTGCTTGGAATCCGTCTGCCCTGCCGCGTATGGCTCTC 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">30 CACCGTTAGACACGTAGAATTGCGCCAGCAGGTGGCAAGGAGGGAGAGCCATACGCGGCA 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">31 CAATTCTACGTGTCTAACGGTGAGCTGTCTTGCATGCTGTACCAGCGTAGCTGCGACATG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">32 CAGGAGGGCGTAAGAAGCGATGTTGAATGGAACACCCAGACCCATGTCGCAGCTACGCTG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">33 GCTTCTTACGCCCTCCTGACCATCCTGATCGCGAAAGCGACCGGCCTCCGCCCAGGTGAA 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">34 ACGTGGTTAGAGTAAACGTGCGCGTCACCCAGGGTATGAACCAGTTCACCTGGGCGGAGG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">35 GCACGTTTACTCTAACCACGTTGAACCGTGCAACGAACAACTCAAACGCGTACCTCGTGC 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">36 TTCCAGAAATTCACGTTCACGACGGAAAACCAGGTACGGAAAGGCACGAGGTACGCGTTT 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">37 CGTGAACGTGAATTTCTGGAAGACTATGAAGAAGGTGACATGGAAGTTATCGACTATGCG 60 <span style="font-family: 'Lucida Console',Monaco,monospace;">38 TTAAACCGCCATTTTCATAGAGATAGGTGGGTACGGCGCATAGTCGATAACTTCCATG 58 [|LOGFILE.txt] upstream: TACTTCCAATCCATG__TCCCTGTTCAAAATCCGTA__ downstream: TATCCACCTTTACTGTTA__AACCGCCATTTTCATAGAGA__ __[|code]__<span class="wiki_link_ext"> [|data]
 * Target (protein/gene name):**
 * NCBI Gene # or RefSeq#:**
 * Gene ID:**
 * Protein ID (NP or XP #) or Wolbachia#:**
 * Organism:**
 * Etiologic Risk Group (see link below):**
 * Background/Disease Information:**
 * Essentiality of this protein:**
 * Complex of enzymes:**
 * EC#:**
 * Link to BRENDA EC# page:**
 * Enzyme Assay information (spectrophotometric, coupled assay ?, reagents):**
 * -- link to Sigma (or other company) page for assay or assay reagents (substrates)**
 * -- link to paper that contains assay information**
 * Structure Available (PDB or Homology model)**
 * -- PDB # or closest PDB entry if using homology model:**
 * -- Query Coverage (if not direct match):**
 * -- Max Ident (if not direct match):**
 * Druggable Target (see Databases for this):**
 * Current Inhibitors:**
 * Expression Information (has it been expressed in bacterial cells):**
 * Purification Method:**
 * Image of protein (PyMol or etc):**
 * Amino Acid Sequence:**
 * length of your protein in Amino Acids**
 * Molecular Weight of your protein in kiloDaltons using the [|Expasy ProtParam] website**
 * Molar Extinction coefficient of your protein at 280 nm wavelength:**
 * CDS Gene Sequence:**
 * GC% Content for gene:**
 * CDS Gene Sequence (codon optimized) - after having done Primer Design:**
 * GC% Content for gene (codon optimized):**
 * Primer design results for pNIC-Bsa4 cloning (list seqeunces of all of your ~60 nt long primers):**
 * DNA Works Output File:**
 * Primer design results for 'tail' primers (this is just 2 sequences):**