Conformational selection mechanism governs oxygen ligation to H-NOX proteins

H-NOX proteins are at present the only structural models available for the study of the ligand binding affinity and selectivity of soluble guanylate cyclase, the physiological receptor of nitric oxide. The oxy complex and resting state structures of two bacterial H-NOX proteins of markedly different oxygen affinity, but of quite similar sequence, were studied by molecular dynamics simulations at 300 K and 400 K. Unexpectedly, the different O2 affinity was found to be reflected in differences of the resting states structures. A conformation containing a pre-formed oxygen-binding cage is the most populated in the resting state equilibrium ensemble of the only successful O2 binder, Tt H-NOX at 300 K, suggesting that conformational selection governs the interaction.

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