High throughput crystallography at SGC Toronto: an overview

The completion of the human genome allows the analysis, for the first time, of biological systems in the context of entire gene families. For enzymes, this approach permits the exploration of complex substrate specificity networks that often exhibit considerable overlap within and between protein families. The case for a family-based approach to protein studies is compelling, given the prospect of exploiting these specificities for various purposes, such as the development of therapeutic reagents. The Structural Genomics Consortium (SGC) was created to determine the structures of proteins with relevance to human health and place the structures into the public domain without restriction on use. The SGC operates out of the Universities of Toronto and Oxford, and Karolinska Institutet, each working on nonoverlapping protein target lists. The SGC focus on human protein families requires a repertoire of crystallography methods that differ from those adopted by structural genomics projects that are focused on filling out protein fold space. The key differences are heavier reliance on in house x-ray sources for diffraction data collection and predominant use of molecular replacement for phase determination. As projects such as the US Protein Structure Initiative and others fill the PDB with representatives of most major fold families, the SGC approach will become an increasingly useful model for many structural biology laboratories in the future. Technical details of the flow of samples and data within the high throughput (HTP) environment at SGC Toronto are presented, and provide a useful paradigm for the organization of collaborative or shared x-ray instrumentation facilities.