GEOMETRY OF METAL-LIGAND INTERACTIONS RELEVANT TO PROTEINS

Marjorie M Harding

Department of Biochemistry, University of Edinburgh, Michael Swann Building, King's Buildings, Edinburgh EH9 3JR, Scotland.

The Cambridge Structural Database (CSD) [1] contains crystallographic data for very large numbers of 'small molecule' compounds whose structures have been accurately determined by diffraction methods, and excellent systems (Quest, Vista) for extracting and studying the geometry of the molecules are provided.

From this database we are assembling information on the geometry of the coordination groups of metals, for metals and ligands which are commonly found in proteins; the information includes interatomic distances, angles, and the orientation of groups such as imidazole, carboxylate relative to the M-N or M-O bonds. This should show both the preferred geometry and the range of allowed geometry. We hope this information may be useful a) for the better understanding of the coordination chemistry of these metals, and thus to their function in protein molecules, and b) in the interpretation of electron density maps and in the refinement of protein structures wherever constraints/restraints are required.

One part of this study has covered Ca, Mg, Mn and Zn complexes with carboxylate groups; Ca complexes are very numerous (64 structures, 248 Ca...carboxylate interactions), zinc complexes moderately common (56 structures, 87 interactions), and magnesium complexes very few in number (8). In the Ca complexes the carboxylate group may be mono- or bidentate, as judged by the Ca...O distances and shown by Einspahr and Bugg [2], and Ca is typically 7 or 8 coordinate to O and N as the other donors. In the zinc complexes, the carboxylate group may be mono- or bidentate or intermediate between mono- and bi-dentate; S and Cl donors are common, as well as N and O; coordination numbers from 4 to 6 are common. These characteristics, which suggest comparable energies for a range of states probably contribute to the effectiveness of Zn at the catalytic site of many enzymes. Earlier studies of carboxylate complexes, and of hydrates of many biologically important metal ions were made by Glusker and colleagues [3,4].

[1] Allen,F.H. & Kennard,O. (1993) Chemical Design and Automation news 8, 1 and 31-37.
[2] Einspahr,H. & Bugg,C.E. (1981) Acta Cryst B36, 264-271.
[3] Carrell,C.J., Carrell,H.L., Erlebacher,J. & Glusker,J.P. (1988) J. Amer. Che, m. Soc. 110, 8651-8656.
[4] Katz,A.K., Glusker,J.P., Beebe,S.A. & Bock,C.W. (1996) J. Amer. Chem. Soc. 24, 5752-5763.