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DNA Topoisomerases in Unicellular Pathogens: Structure, Function, and Druggability.
Somenath Roy Chowdhury1, Hemanta K Majumder1
1Laboratory of Molecular Parasitology, Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India.
Unicellular pathogens possess unique DNA topoisomerases absent in humans, offering new therapeutic targets. This review explores their distinct structures, functions, and potential for drug development against infectious diseases.
Area of Science:
- Molecular Biology
- Biochemistry
- Parasitology
Background:
- DNA topoisomerases are essential enzymes for nucleic acid metabolism in all organisms.
- Specific topoisomerase subtypes found in prokaryotes and some unicellular eukaryotes are absent in higher eukaryotes.
- Pathogenic microbes exhibit unique topoisomerase structures and functions distinct from non-pathogenic counterparts.
Purpose of the Study:
- To review the unique structural and functional attributes of topoisomerases from unicellular pathogens.
- To focus on bacterial and protozoan parasite topoisomerases.
- To summarize progress in targeting these enzymes for therapeutic development.
Main Methods:
- Literature review of existing research on microbial topoisomerases.
- Comparative analysis of topoisomerase structures and functions.
- Assessment of druggability and therapeutic potential.
Main Results:
- Unicellular pathogens harbor distinct topoisomerases with unique molecular architectures.
- These enzymes possess specialized functionalities crucial for pathogen survival.
- Significant progress has been made in identifying druggable targets among these microbial topoisomerases.
Conclusions:
- Topoisomerases from unicellular pathogens represent promising targets for novel antimicrobial therapies.
- Understanding their unique features is key to developing effective treatments against bacterial and protozoan infections.
- Further research into druggability can pave the way for new drug discovery platforms.
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