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Evolution of protein kinase substrate recognition at the active site

Fig 2

Aggregated analysis of sequence divergence across kinase families (left) and subfamilies (right).

For each kinase domain position, the total number of ‘switches’ (score > 95th percentile of scores) was counted across all families or subfamilies considered (see Materials and methods). (Top) Results mapped to kinase structures (mouse protein kinase A: PDB 1ATP). The kinases are represented in complex with an ATP molecule (green, orange, blue, red) and a substrate-mimicking inhibitor (PKIA, yellow). Darker shades of red or blue represent a higher number of switches (see colour bar, right). (Middle) Total number of switches mapped to the kinase primary sequence, with secondary structure elements represented above the bar plot. A domain position is considered to be ‘frequently switching’ if the number of switches lies above a 90th percentile threshold for the kinase domain. The threshold is 8 for families and 7 for subfamilies. (Bottom) The values for each domain position have been grouped according to the functional category (‘catalytic’, ‘regulatory’, ‘proximal’, etc.) and the distribution plotted separately at the family and subfamily level. The numbers in brackets represent the number of residues in each category. PDB, Protein Data Bank; PKIA, cAMP-dependent protein kinase inhibitor alpha; SDR, specificity-determining residue.

Fig 2