* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download doc - University of California, Santa Cruz
Polyadenylation wikipedia , lookup
Biochemistry wikipedia , lookup
Drug discovery wikipedia , lookup
Drug design wikipedia , lookup
Ultrasensitivity wikipedia , lookup
Interactome wikipedia , lookup
Gene expression wikipedia , lookup
G protein–coupled receptor wikipedia , lookup
Epitranscriptome wikipedia , lookup
Biochemical cascade wikipedia , lookup
NADH:ubiquinone oxidoreductase (H+-translocating) wikipedia , lookup
Paracrine signalling wikipedia , lookup
Metalloprotein wikipedia , lookup
Protein structure prediction wikipedia , lookup
Oxidative phosphorylation wikipedia , lookup
Amino acid synthesis wikipedia , lookup
Clinical neurochemistry wikipedia , lookup
Evolution of metal ions in biological systems wikipedia , lookup
Two-hybrid screening wikipedia , lookup
Nuclear magnetic resonance spectroscopy of proteins wikipedia , lookup
Protein–protein interaction wikipedia , lookup
Biosynthesis wikipedia , lookup
Western blot wikipedia , lookup
Enzyme inhibitor wikipedia , lookup
UNDERSTANDING THE MECHANISM OF ACTION OF THE PLASMODIUM FALCIPARUM LARIAT DEBRANCHING ENZYME IN THE INTRON TURNOVER PATHWAY Maria Daleke, Kevin Karplus University of California Santa Cruz 14/02/05 More and more information is gained on pre-mRNA splicing mechanisms, but little is known about the biological and evolutionary significance of introns. We therefore need a simple way of investigating those, and the enzymes involved in the intron turnover pathway. The target enzyme of the study, the RNA lariat debranching enzyme (DBR) from mosquito-borne parasitic protozoan Plasmodium falciparum, participates in the early degradation of introns in lariat conformation by debranching them to enable further degradation by exonucleases. The short term aim is to develop an assay for expressing the enzyme in bacteria, and for expressing the two subunits that build up the protein separately. Thereafter site-directed mutagenesis will be performed based on structural predictions using bioinformatics tools, as no experimental structure determination has been performed on DBR proteins, to examine the functions of the two subunits, and to understand the mechanism of action of the protein. It has been shown in Schizosaccharomyces pombe that intron accumulation cause severe growth effects, and it has been suggested that lariat debranching is a rate-limiting step in the breakdown of introns. This makes the lariat DBR protein a suitable drug target, and by using the P. falciparum DBR enzyme the long term goal of finding a treatment for malaria, a disease that kills 2.7 million people and infects 300 – 500 million people annually, may be fulfilled.