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Flavin-Dependent Thymidylate Synthase as a New Antibiotic Target
Michael Choi1, Kalani Karunaratne2, Amnon Kohen3
1Department of Chemistry, The University of Iowa, Iowa City, IA 52242-1727, USA. michael-a-choi@uiowa.edu.
Molecules (Basel, Switzerland)
|May 24, 2016
Summary
Flavin-dependent thymidylate synthase (FDTS) offers a novel antibiotic target not found in humans. Inhibitors of FDTS could combat bacterial infections by disrupting essential DNA synthesis pathways.
Area of Science:
- Biochemistry
- Molecular Biology
- Medicinal Chemistry
Background:
- Humans synthesize DNA's building block, 2'-deoxythymidine-5'-monophosphate (dTMP), using thymidylate synthase (TSase).
- Pathogenic bacteria utilize flavin-dependent thymidylate synthase (FDTS) for dTMP synthesis, an enzyme absent in humans.
- FDTS presents a potential target for novel antibacterial agents.
Purpose of the Study:
- To review the structural and mechanistic similarities and differences between FDTS and TSase.
- To discuss the potential of FDTS as a therapeutic target for antibiotic development.
Main Methods:
- Comparative analysis of FDTS and TSase structures.
- Review of enzymatic mechanisms.
- Survey of current research on FDTS inhibitors.
Main Results:
- FDTS and TSase share functional roles but differ in structure and cofactors.
- FDTS is essential for certain bacterial pathogens, making it a viable drug target.
- Research is progressing on identifying effective FDTS inhibitors.
Conclusions:
- FDTS represents a promising target for developing new antibiotics against bacterial infections.
- Understanding FDTS structure and mechanism is key to designing potent inhibitors.
- Targeting bacterial FDTS offers a strategy to overcome existing antibiotic resistance.
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