High throughput crystallography at SGC Toronto: an overview

Area of Science:

• Structural biology
• Genomics
• Biochemistry

Background:

• The completion of the human genome enables analysis of biological systems through entire gene families.
• Enzyme studies can explore complex substrate specificity networks with overlapping specificities within and between protein families.

Purpose of the Study:

• To determine the structures of proteins relevant to human health.
• To place protein structures into the public domain without restrictions.
• To develop a family-based approach for protein studies, particularly for therapeutic reagent development.

Main Methods:

• Crystallography methods tailored for human protein families.
• Increased reliance on in-house X-ray sources for diffraction data collection.
• Predominant use of molecular replacement for phase determination.
• High-throughput (HTP) sample and data flow management.

Main Results:

• The SGC's approach differs from structural genomics projects focused on protein fold space.
• The SGC's methods are becoming an increasingly useful model for structural biology laboratories.
• Technical details of HTP workflow at SGC Toronto are presented.

Conclusions:

• A family-based approach to protein studies is compelling for exploiting specificities.
• The SGC's methodology provides a paradigm for collaborative or shared X-ray instrumentation facilities.
• The SGC's work contributes significantly to understanding human health-related proteins.