Enzymatic Studies of a Malarial Drug Target
by MD Phd Tina Dasgupta (9783639130010)

Enzymatic Studies of a Malarial Drug Target

MD Phd Tina Dasgupta

Release Date: 01 April 2009
Format: Paperback
Pages: 112
Category: Biochemistry
Publisher: VDM Verlag
ISBN: 9783639130010
ISBN-10: 3639130014

Plasmodium falciparum is the parasite responsible for more than 90% of deaths caused by the global epidemic of malaria.The enzyme thymidylate synthase- dihydrofolate reductase (TS-DHFR) is a major antimalarial drug target, and mutations in this enzyme have caused widespread resistance.Our work comprises the first systematic, mechanistic characterization of TS-DHFR and its non-active site regions.Our kinetic data show this bifunctional enzyme is regulated by elegant interdomain communication, as well as catalytic contributions from distant structural regions, far from the active sites. Understanding the role of these unique regions may lead to more specific, less toxic therapies.Also, molecular docking and virtual screening of this enzyme identified a lead compound which inhibits both wildtype and drug-resistant parasites.Co-crystal structures of enzyme with compound suggest a molecular basis for overcoming drug resistance.This work demonstrates how in-depth kinetic analyses can be used to identify novel intramolecular targets for rational drug design, and should be useful specially to students of enzymology, protein biochemistry and pharmacology.

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