Macromolecular Structure

Dr. Miroslaw Cygler
Tel.: (514) 496-6321
Fax: (514) 496-5143
E-mail: mirek.cygler@cnrc-nrc.gc.ca
biography

The Macromolecular Structure group aims to develop high throughput methods for determining protein structures, crucial to discovering function and mechanism of action at the molecular level. The group's main efforts are directed towards this goal and encompass both bacterial and mammalian proteins. The group uses X-ray crystallography to determine three-dimensional structures of proteins with emphasis on two research areas: (1) enzymatic mechanisms of potential virulence factors from pathogenic bacteria, and (2) protein-protein complexes essential in signaling networks. The resulting structures will provide an understanding of the catalytic processes at the molecular level; identify parts of the protein essential for activity and substrate specificity and aid in the development of selective and potent inhibitors. The structures of scaffold proteins and their complexes with interacting proteins will be used for designing small molecule inhibitors of protein-protein interactions with the potential to be used in therapeutic interventions.

The research activities of the Macromolecular Structure group are integrated into two main programs, one determining the three-dimensional structures of adapter proteins in complex with their interacting partners from signaling networks and the second providing three-dimensional structures of potential virulence factors from pathogenic bacteria. Both these programs are directed toward the design of specific inhibitors and drug development.

Lunin VV, Munger C, Wagner J, Ye Z, Cygler M, Sacher M (2004) The Structure of the MAPK Scaffold, MP1, Bound to its Partner, p14. A Complex with a Critical Role in Endosomal Map Kinase Signaling. J. Biol. Chem. 279: 23422-23430.

Lunin VV, Li Y, Linhardt RJ, Miyazono H, Kyogashima M, Kaneko T, Bell AW, Cygler M (2004) High-Resolution Crystal Structure of Arthrobacter aurescens Chondroitin AC Lyase: an Enzyme-Substrate Complex Defines the Catalytic Mechanism. J. Mol. Biol. 337: 367-386.

Schrag JD, Bergeron, JJM, Li Y, Borisova S, Hahn M, Thomas DY, Cygler M (2001) The Structure of Calnexin, an ER Chaperone Involved in Quality Control of Protein Folding. Mol. Cell. 8: 633-644.