2021-12-29, 14:00-16:00

• No.5 Scientific building, office 308

Proteins play essential roles virtually in all aspects of the biological systems. In particular, they are key elements for maintaining cell signaling by inter- and intra- protein communication. Among the diversity of protein families, enzymes, the nature’s catalysts, regulate cellular activities through the transformation of metabolic intermediates and the mediation of signaling pathways. Malfunction of many key enzymes will lead to failure of cellular communication, and will cause human diseases such as cancer. Therefore, understanding of how these enzymes work, especially the ones involved in signaling pathways, will provide us valuable knowledge for treating diseases and for the health of human beings. In this context, I will present the mechanistic studies of two classes of enzymes – thiamine diphosphate (ThDP) dependent enzymes in sugar metabolism and S-adenosyl methionine (SAM) dependent methyltransferase. I will first talk about how a special type of hydrogen bonds, termed low-barrier hydrogen bonds (LBHBs), serve as a critical element in the signaling pathways of multiple ThDP-dependent enzymes. We examined the impact of LBHBs through crystallographic analysis of genuine enzymatic intermediates, microscopic interrogation of kinetics and thermodynamics of catalysis, and validated the assignment using computational calculations. Then, I will move to a recently discovered actin histidine methyltransferase SETD3 - the first metazoan protein histidine methyltransferase – and talk about how we identified SETD3 as the first histidine methyltransferase, and how this enzyme adds signaling methyl groups on distinct target substrates. These two examples presented here would highlight how enzymes could exquisitely utilize their structural elements to properly carry out functions. These findings also imply new principles for enzyme design and drug design, and new concepts for treating human diseases, e.g. muscular diseases.