Hydration preferences for Mn4Ca cluster models of photosystem II: location of potential substrate-water binding sites.

Density functional theory calculations are reported on a set of three model structures of the Mn(4)Ca cluster in the water-oxidizing complex of Photosystem II (PSII), which share the structural formula CaMn(4)C(9)H(10)N(2)O(16)·(H(2)O)(n) (q=-1, 0, 1, 2, 3; n=0-7). In these calculations we have explored the preferred hydration sites of the Mn(4)Ca cluster across five overall oxidation states (S(0) to S(4)) and all feasible magnetic-coupling arrangements to identify the most likely substrate-water binding sites. We have also explored charge-compensated structures in which the overall charge on the cluster is maintained at q=0 or +1, which is consistent with the experimental data on sequential proton loss in the real system. The three model structures have skeletal arrangements that are strongly reminiscent, in their relative metal-atom positions, of the 2.9-, 3.7-, and 3.5 Å-resolution crystal structures, respectively, whereas the charge states encompassed in our study correspond to an assignment of (Mn(III))(3)Mn(II) for S(0) and up to (Mn(IV))(3)Mn(III) for S(4). The three models differ principally in terms of the spatial relationship between one Mn (Mn(4)) and a generally robust Mn(3)Ca tetrahedron that contains Mn(1), Mn(2), and Mn(3). Oxidation-state distributions across the four manganese atoms, in most of the explored charge states, are dependent on details of the cluster geometry, on the extent of assumed hydration of the clusters, and in some instances on the imposed magnetic-coupling between adjacent Mn atoms. The strongest water-binding sites are generally those on Mn(4) and Ca. However, one structure type displays a high-affinity binding site between Ca and Mn(3), the S-state-dependent binding-energy pattern of which is most consistent with the substrate water-exchange kinetics observed in functional PSII. This structure type also permits another water molecule to access the cluster in a manner consistent with the substrate-water interaction with the Mn cluster, seen in electron spin-echo envelope modulation (ESEEM) studies of the functional enzyme in the S(0) and S(2) states. It also rationalizes the significant differences in hydrogen-bonding interactions of the substrate water observed in the FTIR measurements of the S(1) and S(2) states. We suggest that these two water-binding sites, which are molecularly close, model the actual substrate-binding sites in the enzyme.