Michael.james

Biography

Understanding the biological functions of proteins, especially those of enzymes, is greatly facilitated by the knowledge of their three-dimensional structures. Our laboratory has a long-standing interest in the hydrolytic mechanisms of the serine and aspartic proteinases and their inhibitors (Maynes et al., 2005; Barrette-Ng et al., 2003a,b; Ng et al., 2000), the glycosyl hydrolases and their transition state mimics lysosomal β-hexosaminidase B (Mark et al., 2003). From these and other studies we have amassed a wealth of structural information for the interpretation of ligand binding specificity, and the chemical pathways for the hydrolysis of good substrates.   One of the major projects in the laboratory is the structural genomics of Mycobacterium tuberculosis . In this project our laboratory has targetted ~400 ORFs from the Mtb genome; we have expressed ~200 of these proteins on a small scale and have expressed ~90 on a mg scale for purification and crystallization. We have crystallized 45 of the purified proteins and have solved the structures of 25 (for example, Maynes et al., 2003; Cherney et al., 2009). We have selected a wide range of proteins and enzymes for our studies.  Many of the first targets did not have an annotated function and our studies have contributed to the determination of their functions.  We have also concentrated on enzymes from a variety of metabolic pathways such as the enzymes of the arginine biosynthesis pathway where we have determined the structures of 6 of the key enzymes.  

Research Interest

Biochemistry