Assembly of Tetrameric Holoenzymes

To understand how any molecule works requires an understanding of its full-length structure and how it is regulated by other molecules. To achieve this goal requires a variety of techniques that include not only Xray crystallography but also solution methods such as small angle Xray and neutron scattering, NMR, fluorescence analyses, and mapping of surfaces by H/D mass spectrometry. All of these approaches have been used to recreate for the first time the structure of a full length tetrameric PKA holoenzyme, and it is only this structure that allows one to begin to fully appreciate the highly allosteric physiological process that leads to the inhibition and activation of PKA.