Water Ligands Regulate the Redox Leveling Mechanism of the Oxygen-Evolving Complex of the Photosystem II

Understanding how water ligands regulate the conformational changes and functionality of the oxygen-evolving complex (OEC) in photosystem II (PSII) throughout the catalytic cycle of oxygen evolution remains a highly intriguing and unresolved challenge. In this study, we investigate the effect of water insertion (WI) on the redox state of the OEC by using the molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) hybrid methods. We find that water binding significantly reduces the free energy change for proton-coupled electron transfer (PCET) from Mn to Y_Z^•, underscoring the important regulatory role of water binding, which is essential for enabling the OEC redox-leveling mechanism along the catalytic cycle. We propose a water binding mechanism in which WI is thermodynamically favored by the closed-cubane form of the OEC, with water delivery mediated by Ca²⁺ ligand exchange. Isomerization from the closed- to open-cubane conformation at three post-WI states highlights the importance of the location of the Mn^III center in the OEC and the orientation of its Jahn-Teller axis to conformational changes of the OEC, which might be critical for the formation of the O-O bond. These findings reveal a complex interplay between conformational changes in the OEC and the ligand environment during the activation of the OEC by Y_Z^•. Analogous regulatory effects due to water ligand binding are expected to be important for a wide range of catalysts activated by redox state transitions in aqueous environments.