|Protein crystallography is a powerful tool capable of revealing atomic details of protein. The technique has been widely used to determine 3-D structures of proteins, multi-domain large protein complexes, protein-DNA interactions etc. Protein crystallography has in the last decade advanced greatly and made a major contribution to the fundamental understanding of biological processes and provided insights into problems of molecular recognition and biological control of importance to medicine and the pharmaceutical industry. In our lab, we are currently focusing on three classes of proteins - antifreeze proteins (supported by CIHR, Ca2+-dependent thiol protease calpain (supported by PENCE) and phosphatase/kinase (supported by NSERC).
Antifreeze proteins are found in a variety of species such as fish, insects and plants. They have the unique capability to bind to ice seed crystals and prevent them from further growth, therefore avoiding and/or lessening the damage to the host. Our research focus is to determine the 3-D structures of these antifreeze proteins and reveal the structural basis for their ice-binding properties.
Calpains have the unique feature in coupling cysteine protease activity and calmodulin-like EF-hands. We have recently determined the first structure of calpain, which reveals an unusual thiol protease fold associated with Ca2+-binding domains. In the absence of Ca2+, the structure shows that the active site is not assembled, suggesting that Ca2+-induced conformational changes move the protease domains to form a functional enzyme.
Phosphatase/kinase are involved in a wide range of cellular processes. Escherichia coli phytase is a member of the histidine acid phosphatase family. Our recently determined structures of the phytase and its complex with phytic acid have revealed a unique mechanism of coupling substrate binding with catalysis.
Ribbon picture of E. coli phytase complexed with natural substrate phytate (Lim et al., Nature Structural Biology, 7:108-133 (2000))