TABLE OF CONTENTS The establishment of a unique H + ion entry point and a defined pathway for proton delivery in RCs are worth discussing in terms of preconceptions about proteins and small molecules. It has been known for decades that proteins are not readily penetrated by small molecules, although it was a somewhat radical idea when first espoused. [177], [178] It became clear from studies of myoglobin that even very weakly polar (CO) or apolar (O 2) molecules could not readily reach the heme binding site except through a specific pathway that was designed for flexibility and access. [179], [180] On the other hand, there are also good indications that water does penetrate into the surface layers of proteins, contributing, among other things, to the non-homogeneous dielectric properties of proteins in a functionally important way [181], [182], [183], [184], [185], [186]. From the latter, it seemed possible that the highly polar nature of the Q B domain could permit proton delivery in a rather non-specific fashion and that no single pathway would be dominant. Water chains, identified in the crystal structures, were suggested as possible proton pathways, [187], [188] but attempts to disrupt these did not result in effects that could be ascribed to proton transfer rates or equilibria. [189], [190], [191] This also seemed to lend some support to a distributed proton delivery network.
However, the identification of the surface...
