Ligand functions, amino acid side chains

In addition to cobalt and iron (discussed above), other metals frequently function as cofactors in enzyme-catalyzed reactions. Like coenzymes, they are useful because they offer something not available in amino acid side chains. The most important of such features of metals are their high concentration of positive charge, their directed valences for interacting with two or more ligands, and their ability to exist in two or more valence states. 

In the protein world structural conservatism and diversity are combined on two different levels conservatism in the more macroscopic, that is, the structural level and diversity on the microscopic level, that is, the individual amino acid sequence. The fold defines the scaffold of the protein, that is, the 3D structure of the amino acid backbone, as well as the shape and size of the active site and the spatial orientation of the catalytic residues. The individual amino acid side chains forming the active site and its catalytic residues determine the molecular interactions between the protein and the ligand. The same fold can be assembled by amino acid sequences with only as little as a few percent sequence similarity. Thus both, fold and sequence, determine together the binding properties of any protein and enable the vast number of specific functions to be carried out by a limited number of fold types. ... 

Some of these sites can effect function in zinc proteins as well as stabilizing structure. The hydrolase class of zinc enzymes are good examples of this action. In this case, one or more amino acid residues within the active site may be provided by the amino acid spacers between zinc ligands (Figure 12). The side chain of these amino acids may be involved in substrate binding, bond cleavage or modulating the chemical enviromnent of the active site. In addition, other active-site residues are often provided by... 

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