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Thymidylate synthase
From Proteopedia
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{{STRUCTURE_4tmk| PDB=4tmk | SIZE=400| SCENE= |right|CAPTION=E. coli thymidylate synthase complex with bisubstrate inhibitor, [[4tmk]] }} | {{STRUCTURE_4tmk| PDB=4tmk | SIZE=400| SCENE= |right|CAPTION=E. coli thymidylate synthase complex with bisubstrate inhibitor, [[4tmk]] }} | ||
| - | + | == Function == | |
| - | + | '''Thymidylate synthase''' (TS) catalyzes the methylation of dUMP to dTMP using 5,10-methylenetetrahydrofolate as a cofactor. TS is essential for DNA replication and repair<ref>PMID:2243092</ref>. In protozoa, dihydrofolate reductase (DHFR) and TS are expressed as a bifunctional monomeric enzyme ('''DHFR-TS)''' with the DHFR entity at the N terminal. DHFR and TS catalyze consecutive reactions in the dTMP biosynthesis. There are two different types of TS – '''ThyA''' and '''ThyX'''. The types differ in their activity and structure. The TS ThyX are flavin-dependent enzymes. | |
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| - | + | == Relevance == | |
| - | + | 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> | |
| - | '''Thymidylate synthase''' (TS) catalyzes the methylation of dUMP to dTMP using 5,10-methylenetetrahydrofolate as a cofactor. TS is essential for DNA replication and repair | + | |
==3D structures of thymidylate synthase== | ==3D structures of thymidylate synthase== | ||
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**[[3ah5]], [[3n3y]] - TS + FAD + UMP – ''Helicobacter pylori'' | **[[3ah5]], [[3n3y]] - TS + FAD + UMP – ''Helicobacter pylori'' | ||
}} | }} | ||
| + | == References == | ||
| + | <references/> | ||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||
Revision as of 08:44, 14 September 2016
Contents |
Function
Thymidylate synthase (TS) catalyzes the methylation of dUMP to dTMP using 5,10-methylenetetrahydrofolate as a cofactor. TS is essential for DNA replication and repair[1]. In protozoa, dihydrofolate reductase (DHFR) and TS are expressed as a bifunctional monomeric enzyme (DHFR-TS) with the DHFR entity at the N terminal. DHFR and TS catalyze consecutive reactions in the dTMP biosynthesis. There are two different types of TS – ThyA and ThyX. The types differ in their activity and structure. The TS ThyX are flavin-dependent enzymes.
Relevance
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.[2]
3D structures of thymidylate synthase
Updated on 14-September-2016
References
- ↑ Kaneda S, Nalbantoglu J, Takeishi K, Shimizu K, Gotoh O, Seno T, Ayusawa D. Structural and functional analysis of the human thymidylate synthase gene. J Biol Chem. 1990 Nov 25;265(33):20277-84. PMID:2243092
- ↑ Rahman L, Voeller D, Rahman M, Lipkowitz S, Allegra C, Barrett JC, Kaye FJ, Zajac-Kaye M. Thymidylate synthase as an oncogene: a novel role for an essential DNA synthesis enzyme. Cancer Cell. 2004 Apr;5(4):341-51. PMID:15093541
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