ABSTRACT
Quantitative Biology: From Molecular to Cellular Systems edited by Michael E. Wall © 2012 CRC Press / Taylor & Francis Group, LLC. ISBN: 978-1-4398-2722-2
11.1 Evolution of Protein Kinases as Regulatory Enzymes . . . . . . . . . . . . . . . . . . . 268 11.1.1 Role of Phosphates in the Regulation of Biology . . . . . . . . . . . . . . . . . . 268 11.1.2 Subdomains of the Eukaryotic Protein Kinase . . . . . . . . . . . . . . . . . . . . .269 11.1.3 Evolution of the Protein Kinase Superfamily . . . . . . . . . . . . . . . . . . . . . . .269 11.1.4 Link between cAMP and Kinase Activation . . . . . . . . . . . . . . . . . . . . . . . 271
11.2 Protein Kinase Structure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273 11.2.1 Structural Motifs in the Kinase Core . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273 11.2.2 Hydrophobic Spines Connect the N-and C-Lobes . . . . . . . . . . . . . . . . . 275 11.2.3 Flanking Regions Are Integrated with the Core . . . . . . . . . . . . . . . . . . . .276
11.3 Assembly of Regulated and Dynamic Molecular Switches . . . . . . . . . . . . . . . . 278 11.3.1 Regulation by Phosphorylation of the Activation Loop . . . . . . . . . . . . . 279 11.3.2 Open and Closed Conformations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279 11.3.3 Recognition of Peptides versus Proteins . . . . . . . . . . . . . . . . . . . . . . . . . 280
11.4 Regulation of PKA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285 11.4.1 Regulatory subunits of PKA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285 11.4.2 cAMP Binding to the Regulatory Subunits . . . . . . . . . . . . . . . . . . . . . . . . 285 11.4.3 Cyclic Nucleotide Binding Domains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286 11.4.4 Regulation of PKA by cAMP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288 11.4.5 Dynamic Features of the CNB Domains . . . . . . . . . . . . . . . . . . . . . . . . . . 290
11.5 Assembly of Tetrameric Holoenzymes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290 11.5.1 Isoform Differences Are Dened by SAXS/SANS: Assembly of a
