title: Structural origins of AGC protein kinase inhibitor selectivities: PKA as a drug discovery tool.
abstract: The era of structure-based protein kinase inhibitor design began in the early 1990s with the determination of crystal structures of protein kinase A (PKA, or cyclic AMP-dependent kinase). Although many other protein kinases have since been extensively characterized, PKA remains a prototype for studies of protein kinase active conformations. It serves well as a model for the structural properties of AGC subfamily protein kinases, clarifying inhibitor selectivity profiles. Its reliable expression, constitutive activity, simple domain structure, and reproducible crystallizability have also made it a useful surrogate for the discovery of inhibitors of both established and emerging AGC kinase targets.
authors.affiliation: Norwegian Structural Biology Center, Department of Chemistry, University of Tromsø, N-9012 Tromsø, Norway.
authors.forename: Espen
authors.initials: E
authors.lastname: Åberg
authors.forename: Bjarte
authors.initials: B
authors.lastname: Lund
authors.forename: Alexander
authors.initials: A
authors.lastname: Pflug
authors.forename: Osman A B S M
authors.initials: OA
authors.lastname: Gani
authors.forename: Ulli
authors.initials: U
authors.lastname: Rothweiler
authors.forename: Taianà M
authors.initials: TM
authors.lastname: de Oliveira
authors.forename: Richard A
authors.initials: RA
authors.lastname: Engh
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013379:Substrate Specificity
chemical_list: D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases