Intrasubstrate steric interactions in the active site control the specificity of the cAMP-dependent protein kinase.
The cAMP-dependent protein kinase catalytic subunit phosphorylates serine residues more efficiently than threonine residues in synthetic peptides. In marked contrast, both amino acids are phosphorylated at similar rates when contained within the appropriate intact protein substrate. The structural basis for the discriminatory behavior observed in small peptides has been investigated and found to be a result of intrapeptide steric interactions in the vicinity of the threonine alcohol moiety. Leu-Arg-Arg-Gly-Thr-Leu-Gly, which is nearly free of these interactions, is phosphorylated at a rate that is almost comparable to its serine-containing counterpart.
Prorok
M
M
Department of Chemistry, State University of New York, Buffalo 14214.
Lawrence
D S
DS
D000595:Amino Acid Sequence; D001665:Binding Sites; D007700:Kinetics; D046911:Macromolecular Substances; D008962:Models, Theoretical; D008970:Molecular Weight; D009842:Oligopeptides / Q000138:chemical synthesis; D010766:Phosphorylation; D011487:Protein Conformation; D011494:Protein Kinases / Q000378:metabolism*; D013379:Substrate Specificity
D046911:Macromolecular Substances; D009842:Oligopeptides; D011494:Protein Kinases