Thymidylate synthase: Difference between revisions

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TS inhibition at its folate-binding site is used in anticancer therapeutic drugs. DHFR-TS inhibitors are potential drug targets against parasite-transferred diseases. TS exhibits oncogene-like activity.<ref>PMID:15093541</ref>

Due to its role in cell division, thymidylate synthase has become a popular target for anticancer drugs. Indirect inhibition of thymidylate synthase by the drug 5-fluorouracil (5-FU) is one of the most used inhibitors for study of TS function. This drug indirectly inhibits TS as it it eventually converted to FdUMP, which forms a covalent complex with both the active site cysteine and CH2H4F. Inhibition of TS halts the production of dTMP and, indirectly, 2'-deoxythymidine-5'-triphosphate (dTTP). Both dTMP and dTTP are essential building blocks for DNA synthesis and their absence halts the ability of cells to replicate their genetic information. This is especially effective in cancer cells that rapidly divide and require large amounts of dTMP and dTTP. <ref>DOI 10.2174/0929867054864868</ref>

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</jmol>

==Inhibition==

Methotrexate, a competitive inhibitor of ~~folates~~, <scene name='49/493689/Inhibited/1'>inhibits</scene> TS.

Methotrexate, a competitive inhibitor competes with folate substrate to bind to the active site of TS. Inhibits the conversion of CH2H4F to H2F. This inhibition stops the conversion of products to reactants, stopping cellular reproduction. <scene name='49/493689/Inhibited/1'>inhibits</scene> TS.

Due to its role in cell division, thymidylate synthase has become a popular target for anticancer drugs. Indirect inhibition of thymidylate synthase by the drug 5-fluorouracil (5-FU) is one of the most used inhibitors for study of TS function. This drug indirectly inhibits TS as it it eventually converted to FdUMP, which forms a covalent complex with both the active site cysteine and CH2H4F. Inhibition of TS halts the production of dTMP and, indirectly, 2'-deoxythymidine-5'-triphosphate (dTTP). Both dTMP and dTTP are essential building blocks for DNA synthesis and their absence halts the ability of cells to replicate their genetic information. This is especially effective in cancer cells that rapidly divide and require large amounts of dTMP and dTTP. <ref>DOI 10.2174/0929867054864868</ref>

</StructureSection>

Thymidylate synthase: Difference between revisions

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@@ Line 11: / Line 11: @@
 TS inhibition at its folate-binding site is used in anticancer therapeutic drugs.  DHFR-TS inhibitors are potential drug targets against parasite-transferred diseases. TS exhibits oncogene-like activity.<ref>PMID:15093541</ref>
-Due to its role in cell division, thymidylate synthase has become a popular target for anticancer drugs. Indirect inhibition of thymidylate synthase by the drug 5-fluorouracil (5-FU) is one of the most used inhibitors for study of TS function. This drug indirectly inhibits TS as it it eventually converted to FdUMP, which forms a covalent complex with both the active site cysteine and CH<sub>2</sub>H<sub>4</sub>F. Inhibition of TS halts the production of dTMP and, indirectly,  2'-deoxythymidine-5'-triphosphate (dTTP). Both dTMP and dTTP are essential building blocks for DNA synthesis and their absence halts the ability of cells to replicate their genetic information. This is especially effective in cancer cells that rapidly divide and require large amounts of dTMP and dTTP. <ref>DOI 10.2174/0929867054864868</ref>
 <StructureSection load='' size='350' side='right' caption='Thymidylate synthase complex with dUMP (PDB entry [[1tsv]])' scene='49/493689/Cv/1'>
@@ Line 40: / Line 38: @@
 </jmol>
 ==Inhibition==
-Methotrexate, a competitive inhibitor of folates, <scene name='49/493689/Inhibited/1'>inhibits</scene> TS.
+Methotrexate, a competitive inhibitor competes with folate substrate to bind to the active site of TS. Inhibits the conversion of CH<sub>2</sub>H<sub>4</sub>F to H<sub>2</sub>F. This inhibition stops the conversion of products to reactants, stopping cellular reproduction.  <scene name='49/493689/Inhibited/1'>inhibits</scene> TS.
+Due to its role in cell division, thymidylate synthase has become a popular target for anticancer drugs. Indirect inhibition of thymidylate synthase by the drug 5-fluorouracil (5-FU) is one of the most used inhibitors for study of TS function. This drug indirectly inhibits TS as it it eventually converted to FdUMP, which forms a covalent complex with both the active site cysteine and CH<sub>2</sub>H<sub>4</sub>F. Inhibition of TS halts the production of dTMP and, indirectly,  2'-deoxythymidine-5'-triphosphate (dTTP). Both dTMP and dTTP are essential building blocks for DNA synthesis and their absence halts the ability of cells to replicate their genetic information. This is especially effective in cancer cells that rapidly divide and require large amounts of dTMP and dTTP. <ref>DOI 10.2174/0929867054864868</ref>
 </StructureSection>