Projects

Novel Kinases and Phosphatases Phosphorylation/dephosphorylation is probably the most crucial chemical reaction taking place in living organisms. It is the basis for the regulatory control of many diverse biological events triggered by extracellular effectors. Moreover, it is a universal element of intracellular signal transduction pathways involved in the control of metabolism, gene expression, cell division and differentiation, development, contraction, transport, locomotion, and learning and memory. We are currently focusing on a number of number of novel kinases and phosphatases including, for example, myosin heavy chain kinase, human ADCKs and Escherichia coli membrane tyrosine kinase (Etk) and AceK. Our determined structure of Etk represents the first tyrosine kinase structure from prokaryotes (see figure on right). It reveals a complete different fold than its mammalian counterparts and a unique activation mechanism.

Ribbon picture of the E. coli tyrosine kinase structure.

Structural Genomics of Bacterial Proteins

Infectious microbial diseases remain a persistent public health problem, causing significant loss of life and high economic costs, despite the availability of new vaccines for their prevention and an array of antibiotics for treatment. The problem of ever increasing bacterial resistance to antibiotics continues to grow, and represents an enormous challenge to the biomedical community. We study bacterial pathogens, including E. coli EHEC/EPEC, Legionella and Pseudomonas. Our main goal is to provide a molecular basis for understanding the processes underlying bacterial infection and, in particular, the interaction between bacterial pathogens and their host. Structural biology plays an essential role in attaining this level of understanding and translating the macroscopic view of host-pathogen interactions into a three-dimensional picture of molecules in action. We characterize protein-protein interactions and investigate intracellularly injected proteins (effectors) and their interactions with host proteins. We will pursue functional roles of effectors, their interactions with host proteins and three-dimensional structures of the effectors and effector-target complexes essential for bacterial virulence.