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Comprehensive molecular insights into a specific disease most often require whole pathways and processes to be considered. Structural biology together with complementing biochemical studies is the major means for achieving detailed insight into the molecular mechanisms of proteins in such pathways: how they interact, how they are regulated, and how enzymes recognize and transform substrates. This information provides a knowledge basis for current target drug design efforts and the structural information can directly assist in the rational drug design cycle. The Structural Genomics Consortium (SGC) is an Anglo-Canadian-Swedish consortium pursuing a systematic effort at generating structural insights into proteins of disease related pathways and structural families. At the SGC-Stockholm node, “the little brother” in the consortium, some 430 proteins are currently studied within areas such as; receptor signaling (Toll-, TGF-betaand RTK-receptor based signalling), apoptosis signaling, phosphoinositol and other lipid signaling, ATPases (RNA-helicases and AAA-ATPases), poly-ADP ribose polymerase, as well as nucleotide and amino acid metabolism. Many of the proteins targeted are implied in diseases such as; cancer, inflammatory and infectious diseases. Approximately 70 novel human structures, plus follow-up structures, have been determined in the last three years at SGC-Stockholm. The specific structural genomic strategy applied on some of the pathways and families motioned above will be discussed, as well as examples of structural insights generated by this strategy.

Structural genomic of protein families and pathways in human disease