Study of the energy landscape of a photoactivated adenylate cyclase by high-pressure crystallography

cAMP (Adenosine 3',5' cyclic monophosphate) is a key second messenger in numerous signal trans¬duction pathways, regulating various cellular functions. Modulating its cellular concentration has emerged in the focus of modern optogenetic applications putting forward the photoactivated adenylyl cyclases (PACs) in the optogenetics toolbox. PACs are light-activated enzymes that combine the capacity of a photoreceptor with that of an adenylyl cyclase; the latter being an enzyme responsible for the conversion of ATP (adenosine 5' triphosphate) to cAMP. We propose to use high-pressure macromolecular crystallography to study the energy landscape, conformational fluctuations and breathing motions between sub-states of the photoactivated adenylate cyclase (PAC) from the cyanobacterium Oscillatoria acuminata (OaPAC) in order to explore the allosteric transitions between its conformational states.