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Oligomer Formation of the Bacterial Second Messenger c-di-GMP: Reaction Rates and Equilibrium Constants Indicate a Monomeric State at Physiological Concentrations

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journal contribution
posted on 18.01.2012, 00:00 by Martin Gentner, Martin G. Allan, Franziska Zaehringer, Tilman Schirmer, Stephan Grzesiek
Cyclic diguanosine-monophosphate (c-di-GMP) is a bacterial signaling molecule that triggers a switch from motile to sessile bacterial lifestyles. This mechanism is of considerable pharmaceutical interest, since it is related to bacterial virulence, biofilm formation, and persistence of infection. Previously, c-di-GMP has been reported to display a rich polymorphism of various oligomeric forms at millimolar concentrations, which differ in base stacking and G-quartet interactions. Here, we have analyzed the equilibrium and exchange kinetics between these various forms by NMR spectroscopy. We find that the association of the monomer into a dimeric form is in fast exchange (