Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Molecular evolution wikipedia , lookup
Nucleic acid analogue wikipedia , lookup
Butyric acid wikipedia , lookup
Catalytic triad wikipedia , lookup
Enzyme inhibitor wikipedia , lookup
Bottromycin wikipedia , lookup
List of types of proteins wikipedia , lookup
Metalloprotein wikipedia , lookup
Biochemistry wikipedia , lookup
Title of Project : Functional and structural relationship of Cst-II sialyltransferases to synthesize mono- and disialylated lipo-oligosaccharides derivatives Name of Supervisor : Prof. Nobuhiro Yuki Contact Details: Department of Medicine/Microbiology Level 9, MD6, 14th Medical Drive, NUS, Singapore – 117599. Telephone no: 65161092. Email: [email protected] Short Description Sialyltransferases are enzymes responsible for the transfer of sialic acid to the terminal nascent oligosaccharides. The sialyltransferase in Campylobacter jejuni (Cst-II) is capable of transferring sialic acid moiety from cytidine-5monophospho-N-acetyl-neuraminic acid (CMP-NeuAc) to the terminal position of lipo-oligosaccharides (LOS), thus mimicking the human ganglioside. There are two Cst-II isoforms that has either mono functional (α2,3-sialyltransfearse) or bi functional (α2,3- and α2,8-sialyltransferase) activity. These synthesize different types of gangliosides-like LOS that give rise to different phenotypes of autoimmune diseases. We propose to elucidate structural basis of mono- and bi- functional sialyltransferase activity of Cst-II enzyme and also to obtain novel sialyltransferases that are able to synthesize specific oligosaccharides. The techniques involved in this project would be: recombinant DNA technology and 2-stage site directed mutagenesis, protein expression and detection techniques, kinetic assay and capillary electrophoresis to determine the enzymatic activity of novel Cst-II. On completion of the project, the elucidation of Cst-II molecular mechanism would be helpful in understanding similar enzyme that synthesizes cellsurface glyco-conjugates resulting in autoimmune diseases. The identification of the catalytic residues would enable us to design inhibitors that limit the bacterial ability to synthesize ganglioside-like LOS thus preventing immune evasion.