Zinc coordination sphere in biochemical zinc sites

Zinc is known to be indispensable to growth and development and transmissio n of the genetic message. It does this through a remarkable mosaic of zinc binding motifs that orchestrate all aspects of metabolism. There are now ne arly 200 three dimensional structures for zinc proteins, representing all s ix classes of enzymes and covering a wide range of phyla and species. These structures provide standards of reference for the identity and nature of z inc ligands in other proteins for which only the primary structure is known . Three primary types of zinc sites are apparent from examination of these structures: structural, catalytic and cocatalytic. The most common amino ac ids that supply ligands to these sites are His, Glu, Asp and Cys. In cataly tic sites zinc generally forms complexes with water and any three nitrogen, oxygen and sulfur donors with His being the predominant amino acid chosen. Water is always a ligand to such sites. Structural zinc sites have four pr otein ligands and no bound water molecule. Cys is the preferred ligand in s uch sites. Cocatalytic sites contain two or three metals in close proximity with two of the metals bridged by a side chain moiety of a single amino ac id residue, such as Asp, Glu or His and sometimes a water molecule. Asp and His are the preferred amino acids for these sites. No Cys ligands are foun d in such sites. The scaffolding of the zinc sites is also important to the function and reactivity of the bound metal. The influence of zinc on quate rnary protein structure has led to the identification of a fourth type of z inc binding site, protein interface. In this case zinc sites are formed fro m ligands supplied from amino acid residues residing in the binding surface of two proteins. The resulting zinc site usually has the coordination prop erties of a catalytic or structural zinc binding site.