Biochemical and structural characterization of a type 2 ribosome-inactivating protein from viscum ovalifolium

Plant ribosome-inactivating proteins (RIPs) are translation inhibitors, which have biological function in their defense systems. Extracts from various Viscum (mistletoe) species have been used as immunomodulating and alternative cancer therapeutic agents. Lectin of mistletoe species (a typical type 2 RIPs) is a major constituent responsible for their pharmacological effects. This study focuses on the biochemical and molecular characterization of a novel mistletoe lectin isolated from Viscum ovalifolium, a Singapore-specific mistletoe species, which we named Singapore mistletoe lectin (SML). De novo protein sequencing of SML and its cDNA cloning allowed us to obtain SML in recombinant protein forms, demonstrating that the SML-A chain is a potential anticancer agent while SML-B chain has an inhibitory effect against dengue viral infection. There are two significant findings from this study with regards to the anti-dengue effect: (1) the inhibition of all four serotypes of DENV by SML and (2) potential mechanistic insights into the SML-B-chain-mediated inhibitory effect against DENV.​Doctor of Philosophy (SBS