[Untitled]

The binding of two metal ions that are in close proximity in proteins is examined using a combination of (1) crystallographic structural database analyses and (2) density functional theory calculations on model complexes. Divalent magnesium and manganese ions are the focus of the present study. It is found that in all proteins in the Protein Databank that have two closely positioned magnesium or manganese ions, these metal ions are generally bridged by at least one negatively charged oxygen-containing group—carboxylate, phosphate, or sulfate. This group transfers (negative) electron density to the metal ions and this helps to reduce electrostatic repulsion in the region. The geometry of the two-metal complex appears to depend on the nature of the negatively charged group between them. When a single oxygen atom is also in a bridging position, the two metal ions are found to be closer together than when only a carboxylate group binds them together. This suggests that this bridging oxygen atom may be negatively charged, e.g., a hydroxide ion rather than a water molecule. Details of the geometry of such bridges and the relevant motifs that are found in crystal structures are described.