The 'unique' metal-binding properties of metalloenzymes

Abstract

ABSTRACT(1) The theme of the survey is that metalloenzymes represent rather 'unique' metal complexes when compared to the simpler system generally studied by coordination chemists. This theme is introduced by a brief presentation of the historical development of the metalloenzyme field, particularly the contributions of 0. Warburg and D. Keilin.(2) Various types of metal ion-protein interactions and the distinction between non-specific and specific binding have been briefly reviewed.(3) The ·unique' properties in the specific interactions with metalloenzymes are illustrated by a discussion of three different enzymes: carboxypeptidase, carbonic anhydrase and laccase (p-diphenol oxidase). In conclusion it is suggested that in these enzymes the 'unique' coordination imparts properties to the metal ion facilitating its role in the catalytic reaction. METALLOENZYMES AND MODELSThe study of the role of metal ions in enzyme reactions provides a beautiful example of an area in which increased understanding has been intimately connected with the close interaction between traditionally distinct disciplines. Thus, the techniques and results of coordination chemistry, a field generally regarded as a branch of inorganic chemistry, have been utilized in investigations on one of the central problems of biochemistry, that of the relation between structure and function of enzymes. To my mind, a major impression from the progress made so far isthat metalloenzymes represent rather 'unique' metal complexes in comparison with the simpler systems generally studied by coordination chemists. The nature of these 'unique' metal-binding properties and their relation to the catalytic function of the metal ion in a number of metalloenzymes will form the main theme of this survey.The unusual coordination chemistry of metalloenzymes necessitates that arguments based on the properties of simpler 'model' complexes must be applied with caution and considerable judgement. This apparent antithesis between enzymes and models is weil illustrated by the different attitudes taken by two investigators, D. Keilin and 0. Warburg, who both played prominent roles in the early development of the field. Thus, it may be appropriate to introduce the subject by a brief account of some main points in the history of metalloenzymes.G. Bertrand was the first investigator who suggested a metal as the active group in enzymes. This occurred in the 1890s in connection with his work on