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Structure, Expression, and Function of Malaria Intron Debranching Enzyme
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The main objective of this project is molecular and biochemical
characterization of metallophosphoesterase superfamily of enzyme in
malaria parasite involved in pre-mRNA processing which requires a
transition metal ion for its catalytic activity. A twofold approach was
designed to study the enzyme. We have identified such enzyme by
comparative genomics from malaria genome. The gene was cloned into a
bacterial expression vector to attempt the recombinant expression,which
could then be purified and used for in vitro biochemical characterization
and also for crystallization/x-ray diffraction structural analysis. The
gene was also introduced into a heterologous yeast system in an attempt to
integrate the gene into the yeast genome; this strain could then be used
for in vivo functional and biochemical assays. This strategy could allow
drug-targeting of the malaria parasite specific domain of the
enzyme that would be innocuous to the host organism.
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Mario Giovacchini
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