-12- - Zinc: Lewis Acid and Gene Regulator

Abstract

Zinc is the second most abundant trace element in the human body. It is essential for growth and development in all forms of life, and has been proposed to have beneficial therapeutic and preventative effects on infectious diseases, including a shortening of the length of the common cold in man. Zinc is found in more than 300 enzymes, where it plays both a catalytic and a structural role. It is the only metal to have representatives in each of the six fundamental classes of enzymes. Zn is also widely involved in the regulation of the transcription and translation of the genetic message. The bioinorganic chemistry of zinc is dominated by a number of factors. The divalent zinc ion is redox inactive, in contrast, for example, to manganese, iron and copper. Zn2+ has no ligand field constraints on its coordination geometry. Coordination number and geometry are therefore dictated only by ligand size and charge. However, in most zinc proteins there is a strong preference for tetrahedral coordination, frequently slightly distorted, which enhances both the Lewis acidity of the zinc centre and the acidity of a coordinated water molecule. Only Cu(II) is a better Lewis acid. Zinc is of borderline hardness; therefore it can bind oxygen, nitrogen and sulfur ligands. Zinc enzymes also participate in the cleavage of the phosphodiester bonds in both DNA and RNA, and their role extends beyond catalysis of hydrolytic reactions to include the important lyase, carbonic anhydrase and the oxidoreductase, alcohol dehydrogenase.