1. Structural origins of AGC protein kinase inhibitor selectivities: PKA as a drug discovery tool
- Author
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Espen Åberg, Richard A. Engh, Taiana Maia de Oliveira, Osman A. B. S. M. Gani, Alexander Pflug, Ulli Rothweiler, and Bjarte Aarmo Lund
- Subjects
Subfamily ,Drug discovery ,medicine.drug_class ,Kinase ,Clinical Biochemistry ,Molecular Sequence Data ,Biology ,Protein kinase inhibitor ,Biochemistry ,Cyclic AMP-Dependent Protein Kinases ,Substrate Specificity ,Phosphotransferase ,chemistry.chemical_compound ,Adenosine Triphosphate ,chemistry ,Drug Discovery ,medicine ,Humans ,Amino Acid Sequence ,Protein kinase A ,Molecular Biology ,Peptide sequence ,Adenosine triphosphate ,Protein Kinase Inhibitors - 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.
- Published
- 2012