Substrate recognition mechanism of human beta-adrenergic receptor kinase 1 based on a three-dimensional model structure
Iino, M.; Shibano, T.
Drug Design and Discovery 14(2): 145-155
Although its detailed substrate specificity is not precisely known, beta-adrenergic receptor kinase 1 phosphorylates beta 2-adrenergic receptors and other G protein-coupled receptors. To elucidate the ligand recognition mechanism of the enzyme and the consensus sequence required for substrates, a three-dimensional structure of the catalytic domain of the enzyme was modeled based on the X-ray crystal structure of the catalytic subunit of cyclic AMP-dependent protein kinase A. When the phosphorylation residue of the substrate was defined as the p position in the model of beta-adrenergic receptor kinase 1, the present study suggested that the consensus sequence recognized by this enzyme would consist of a basic residue at p-3 and an acidic residue at p-2.