Geometry of metal-ligand interactions in proteins

The geometry of metal-ligand interactions in proteins is examined and compa red with information for small-molecule complexes from the Cambridge Struct ural Database (CSD). The paper deals with the metals Ca, Mg, Mn, Fe, Cu, Zn and with metal-donor atom distances, coordination numbers and extent of di stortion from ideal geometry (octahedral, tetrahedral etc.). It assesses th e agreement between geometry found in all metalloprotein structures in the Protein Data Bank (PDB) determined at resolution less than or equal to 1.6 Angstrom with that predicted from the CSD for ligands which are analogues o f amino-acid side chains in proteins [Harding (1999), Acta Cryst. D55, 1432 -1443; Harding (2000), Acta Cryst. D56, 857-867]. The agreement is reasonab ly good for these structures but poorer for many determined at lower resolu tion (examined to 2.8 Angstrom resolution). For metal-donor distances, the predictions from the CSD, with minor adjustments, provide good targets eith er for validation or for restraints in refinement of structures where only poorer resolution data is available. These target distances are tabulated a nd the use of restraints is recommended. Validation of angles or the use in refinement of restraints on angles at the metal atom is more difficult bec ause of the inherent flexibility of these angles. A much simplified set of parameters for angle restraints with quite large standard deviations is pro vided. (Despite the flexibility of the angles, acceptable and preferred coo rdination numbers and shapes are well established and a summary table is pr ovided.) An unusual and perhaps biochemically important feature of Zn coord ination with carboxylate seen in the CSD examples is also clearly present i n metalloprotein structures. With metals like Ca, carboxylate coordination is monodentate or bidentate (two M-O bonds of nearly equal length). In Zn c arboxylates a continuous range between monodentate and bidentate coordinati on is found, with one Zn-O bond of normal length and another of any length between this and a van der Waals contact.