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Vol 9 No 2

MU Faculty of Science Establishes 'Center for Excellence in Protein Structure and Function'

by Prof. M.R. Jisnuson Svasti,
Department of Biochemistry, Faculty of Science

     Bioscience is making rapid advances that will have tremendous impacts on the health and welfare of mankind. In particular, the completion of the Human Genome sequence provides information on the genes present in the human species. However, this is not enough to allow us to understand living processes in human beings. The DNA sequences in the genome must be expressed as proteins before they can perform their designated functions. Indeed, the estimated 30,000 genes in the human genome can give rise to more than 200,000 different proteins. These proteins must fold into their specific three-dimensional structures that determine how they function. In addition, some proteins may be chemically modified after synthesis or converted from inactive to active forms. Moreover, different proteins may be synthesized in different tissues, or at different stages of development or in disease states. Thus, the complete understanding of living processes requires understanding of structure and function relationships in proteins.

     For this reason, MU's Faculty of Science has established the 'Center for Excellence in Protein Structure and Function' as an interdisciplinary research laboratory aiming towards elucidating the molecular basis of protein action and its relationship with three-dimensional structure. Staff in the Center come from various departments, namely Professor M.R. Jisnuson Svasti (Head), Dr. Jirundon Yuvaniyama and Dr. Pimchai Chaiyen from the Biochemistry Department, Dr. Palanpol Kongsaeree from the Chemistry Department, and Dr. Pramvadee Wongsaengchantra from the Biotechnology Department.

     The Center will use a combination of structural biology, protein biochemistry, and mechanistic enzymology to study protein structure-function relationships. Modern and sophisticated equipment, provided by the Faculty of Science, will be available within the Center, including X-ray diffractometer system for studying the three-dimensional structure of proteins and stopped-flow spectrophotometry for studying enzyme mechanisms. The complementarity in expertise of staff members and state-of-the-art equipment will enable the Center to tackle interesting problems at the interface of biochemistry and chemistry. Staff in the Center not only collaborate with other staff at MU, but also with other institutions throughout Thailand and overseas.

Electron density map of part of the structure of a protein,
with protein crystal as inset.

     Current research covers five main areas. The first involves plant glycosidase enzymes that hydrolyze carbohydrate compounds, such as oligosaccharides and glycosides. The molecules can function in cellular recognition, or act as components of drugs, toxins, antibiotics, flavors and scents. Novel enzymes have been isolated such as Thai Rosewood beta-glucosidase, and novel reactions have been found for known enzymes, such as cassava linamarase. The second area is the study of drug targets in malaria, with the aim to develop potent inhibitors for treatment of malarial infection. This includes determining the three-dimensional structure of parasite dihydrofolate reductase-thymidylate synthetase involved in pyrimidine biosynthesis, in collaboration with BIOTEC, and parasite plasmepsin which degrades hemoglobin in the red blood cell. The third area covers enzymes in the synthesis of penicillin derivatives, which are still being imported from overseas at considerable cost. One project attempts to engineer a novel enzyme cephalosporin acylase by mutagenesis. The other project aims to determine the three-dimensional structure of D-phenylglycine aminotransferase, which catalyzes an unusual stereoinversion reaction. The fourth area is the study of mechanism of flavin-containing oxygenase enzymes, especially those acting on aromatic compounds, since they may be useful for bioremediation of aromatic waste. The last area involves searching for enzymes that digest the protein sericin in silk without degrading the major protein fibroin. Such an enzyme will allow new processes to be developed for degumming silk under milder conditions.

     Although the Center strives towards academic excellence in basic science, our research also has social and economic implications, which are of national importance. The Center is also ready to collaborate with other scientists with other research problems, so that Thailand may take advantage of the opportunities raised by the modern bioscience revolution.