Photosystem II (PSII) catalyzes light-driven water oxidation at its oxygen-evolving complex (OEC), a Mn 4 CaO 5 cluster advancing through redox intermediates known as the Kok cycle (S 0 -S 4 ). At each transition, the OEC is activated when pigment P D1 oxidizes the redox-active tyrosine Y Z , and the resulting Y Z • withdraws an electron from a Mn in the cluster. A central mechanistic step is the S 2 to S 3 transition, where Y Z oxidation is coupled to a long-range deprotonation and water insertion at the OEC. Experimental probes provide significant pictures for this step: time-resolved serial femtosecond crystallography (TR-SFX) reveals electron density changes near Y Z , with features at 1 μs indicating Y Z oxidation, and their disappearance by ∼30 μs interpreted as Y Z • reduction. By contrast, kinetic methods, including photothermal beam deflection, X-ray absorption spectroscopy, and electron paramagnetic resonance, place electron transfer from Mn to Y Z • at ∼300 μs, with proton transfer at ∼30 μs.We reconcile these discrepancies by combining quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics (MD) simulations. Our results show that oxidation of P D1 and Y Z disrupts the local hydrogen-bond network, generating perturbations that propagate to trigger deprotonation like an allosteric process. These changes reproduce the TR-SFX density features observed at 1–30 μs without requiring Y Z • reduction, consistent with kinetic assignments of deprotonation at ∼30 μs. We further demonstrate that deprotonation enables water insertion, which lowers the free-energy cost of electron transferring from Mn to Yz • by 6.6 kcal/mol and thereby regulates the redox-leveling mechanism essential for catalytic turnover. Together, these findings reveal how redox events and hydrogen-bond rearrangements couple to drive long-range proton transfer and ligand binding in PSII. More broadly, they illustrate how protein dynamics and allosteric hydrogen-bond networks regulate energy conversion, providing a framework for understanding redox-driven processes in biological catalysis.
Liu et al. (Sun,) studied this question.