Substrate recognition mechanism of human beta-adrenergic receptor kinase 1 based on a three-dimensional model structure.
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.
Iino
M
M
Basic Technology Research Laboratories, Tokyo R&D Center, Daiichi Pharmaceutical Co., Ltd, Japan.
Shibano
T
T
D000595:Amino Acid Sequence; D001665:Binding Sites; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D051552:beta-Adrenergic Receptor Kinases
D010446:Peptide Fragments; C518603:protein kinase inhibitor peptide (5-24); D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases