Cobalt -substituted zinc proteins

Varying ratios of the ligands 7V-(2-thiophenyl)-2,5-dimethylpyrrole and V-methylimidazole were used to form tetrahedral zinc complexes with S4, S3N, and S2N2 coordination spheres. X-ray structural analyses and IR spectra were recorded for all compounds and the relevance to zinc finger proteins was discussed. The comparison to cobalt and cadmium structures showed only minor differences, supporting the theory that changes on substituting these metals into zinc proteins would be minor.538... 

Table I lists isomorphous replacements for various metalloproteins. Consider zinc enzymes, most of which contain the metal ion firmly bound. The diamagnetic, colorless zinc atom contributes very little to those physical properties that can be used to study the enzymes. Thus it has become conventional to replace this metal by a different metal that has the required physical properties (see below) and as far as is possible maintains the same activity. Although this aim may be achieved to a high degree of approximation [e.g., replacement of zinc by cobalt(II)], no such replacement is ever exact. This stresses the extreme degree of biological specificity. The action of an enzyme depends precisely on the exact metal it uses, stressing again the peculiarity of biological action associated with the idiosyncratic nature of active sites. (The entatic state of the metal ion is an essential part of this peculiarity.) Despite this specificity, the replacement method has provided a wealth of information about proteins that could not have been obtained by other methods. Clearly, there will often be a compromise in the choice of replacement. Even isomorphous replacement that should retain structure will not necessarily retain activity at all. However, it has become clear that substitutions can be made for structural studies where the substituted protein is inactive (e.g., in the copper proteins and the iron-sulfur proteins). It is also possible to substitute into metal coenzymes. Many studies have been reported of the...

The substitution of cobalt for the native zinc ions of alkaline phosphatase results in an active enzyme with distinctive optical properties, generated by the interaction of cobalt with the ligands of the protein. These properties may be employed to investigate the modes of binding of cobalt to the enzyme and also serve in a remarkable fashion to distinguish the catalytically essential metal atoms from those which play only a structural role. 

Cobalt(ll) acts as an activating cation or a cofactor in a variety of enzymes, which could thus be directly probed using Co doping and EMS measurements. Moreover, Co has also been shown to be applicable as an isostructural substitute, for example for Zn + in many zinc-containing proteins [43], and even to enhance enzyme s beneficial properties (see, for example. Refs 48,49 and references therein). 

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