Figure 6

Multiple alignment of the binding site regions across PKA orthologue sequences. Starting with the mouse sequence (accession NP_032880) of the protein in the crystal structure 1JLU [92], we searched for orthologues of the catalytic subunit of PKA with the ANNOTATOR suite [45]. In the alignment (generated with T-COFFEE [94]), we present 40 variants thereof ranging as far as from yeast to human (sequence position numbering is without leading methionines according to the 1.29 Å rule [56,57]). The figure focuses on the protein polypeptide stretch that encompasses the residues forming the surface of the binding site at substrate position from -3 to +1. Red triangles (at Glu127, Glu170 and Glu230 in the numbering of 1JLU without the leading methionine in NP_032880) mark positions that form the pocket for substrate residues -3 and -2. Blue triangles (at Leu198, Pro202 and Leu205) mark the hydrophobic pocket-forming positions that accept substrate residue +1 [4–7].