Classification of Protein Kinases Influenced by Conservation of Substrate Binding Residues

Abstract

With the advent of genome sequencing projects in the recent past, several kinases have come to light as regulating different signaling pathways. These kinases are generally classified into different subfamilies based on their sequence similarity with members of known subfamilies of kinases. A functional association is then defined to the kinase based on the subfamily to which it has been characterized. However, one of the key factors that give identity to a kinase in a subfamily is its ability to phosphorylate a given set of substrates. Substrate specificity of a kinase is largely determined by the residues at the substrate binding site. Though in general the sequence similarity based measure for classification more or less gives the preliminary idea on subfamily, understanding the molecular basis of kinase substrate recognition could further refine the classification scheme for kinases and render a better understanding of their functional role. In this analysis we emphasize on the possibility of using putative substrate binding information in the classification of a given kinase into a particular subfamily.