Molecular Basis for the pH Dependent Structural Transition of Nitrophorin 4

MARCELO A. MARTI; DARIO A ESTRIN; ADRIÁN E. ROITBERG

JOURNAL OF PHYSICAL CHEMISTRY B

ACS

Año: 2009 p. 2135 - 2142

1089-5647

Allostery can be defined in a broad sense as a structural change in a protein. The theoretical framework forallostery includes several formulations. In the stereochemical view, the activation event causes a localconformational change that is propagated through residue-to-residue contacts to the rest of the protein throughwell-defined structural pathways. The thermodynamic, or population shift model, instead implies that the“activated conformation” is already present with non-negligible population in the nonactivated conformationalensemble, and therefore the activation merely shifts the equilibrium. Nitrophorins (NPs) are heme proteinsthat store and transport NO in a pH dependent manner, due to a conformational change. Using MD simulations,we show that the NP structural transition occurs in two different conformational free energy landscapes, eachone corresponding to a pH condition and characterized by specific residue-residue interactions that characterizethem. We also show that when the protonation state of the equilibrium state is modified the conformationbecomes unstable and proceeds very fast to an intermediate stable state that is different for each pH condition.Finally, we will discuss that allosteric transition in NP4 does not occur due to a change in the relative populationof both end states, but due to a drastic change in the free energy landscape of its conformational ensemble.