User:Michael O'Shaughnessy/ TS

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== Overview ==
== Overview ==
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This page is a work in progress during the spring 2022 semester.
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The enzyme Thymidylate Synthase (TS) catalyzes the transfer of a methyl group and a hydride from 5,10-methylenetetrahydrofolate to 2-deoxyuridine-5'-monophosphate, resulting in the formation of thymidine 5'-monophosphate and dihydrofolate. This is the only de novo source of dTMP (a precursor to Thymine) in humans. <ref>DOI 10.1021/acs.biochem.1c00063</ref>
The enzyme Thymidylate Synthase (TS) catalyzes the transfer of a methyl group and a hydride from 5,10-methylenetetrahydrofolate to 2-deoxyuridine-5'-monophosphate, resulting in the formation of thymidine 5'-monophosphate and dihydrofolate. This is the only de novo source of dTMP (a precursor to Thymine) in humans. <ref>DOI 10.1021/acs.biochem.1c00063</ref>
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<StructureSection load= '7jxf' size='340' side='right' caption='Caption for this structure' scene=''>
<StructureSection load= '7jxf' size='340' side='right' caption='Caption for this structure' scene=''>
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This is a default text for your page '''Michael O'Shaughnessy/ TS'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.
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You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
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<scene name='90/907470/Ts/1'>Text To Be Displayed</scene>
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Revision as of 15:04, 8 April 2022

Contents

Overview

This page is a work in progress during the spring 2022 semester.


The enzyme Thymidylate Synthase (TS) catalyzes the transfer of a methyl group and a hydride from 5,10-methylenetetrahydrofolate to 2-deoxyuridine-5'-monophosphate, resulting in the formation of thymidine 5'-monophosphate and dihydrofolate. This is the only de novo source of dTMP (a precursor to Thymine) in humans. [1]

2-deoxyuridine-5'-monophosphate(dUMP) + 5, 10-methylenetetrahydrofolate(CH2H4F) ⇌ thymidine 5'-monophosphate(dTMP) + Dihydrofolate(H2F)

Disease

Relevance

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 shuts down 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. [2]


Caption for this structure

Drag the structure with the mouse to rotate

References

  1. ↑ Kholodar SA, Finer-Moore JS, Swiderek K, Arafet K, Moliner V, Stroud RM, Kohen A. Caught in Action: X-ray Structure of Thymidylate Synthase with Noncovalent Intermediate Analog. Biochemistry. 2021 Apr 8. doi: 10.1021/acs.biochem.1c00063. PMID:33829766 doi:http://dx.doi.org/10.1021/acs.biochem.1c00063
  2. ↑ Costi MP, Ferrari S, Venturelli A, Calo S, Tondi D, Barlocco D. Thymidylate synthase structure, function and implication in drug discovery. Curr Med Chem. 2005;12(19):2241-58. doi: 10.2174/0929867054864868. PMID:16178783 doi:http://dx.doi.org/10.2174/0929867054864868
  3. ↑ doi: https://dx.doi.org/10.1016/S1074-5521(01)00067-9

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Michael O'Shaughnessy

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