Patterns of divergence in homologous proteins as indicators of secondary and tertiary structure: a prediction of the structure of the catalytic domain of protein kinases

Abstract

The secondary structure and elements of tertiary structure have been predicted for the catalytic domain of protein kinases using a method that extracts structural information from the patterns of conservation and variation in an alignment of homologous proteins. The central features of this structural prediction are: (a) the catalytic domains of protein kinases do not incorporate a Rossmann fold; (b) the core of the structure is founded on beta sheets built from pairs of bent antiparallel beta strands; (c) five helices, including an especially long helix (alignment positions 129-152) that lie on the outside of the folded core. These proteins are important in many aspects of metabolic regulation.