The biochemistry and enzymology of zinc enzymes

Abstract

Zn2+ is an essential transition metal ion for the life cycle of all living organisms. This metal ion plays key roles in stabilizing proteins, as a cellular messenger, but it is mostly present as an essential cofactor in enzymes. The intracellular levels of Zn2+ are tightly regulated to prevent adventitious zinc binding to other metalloproteins, to limit its toxic effects at high concentrations, and (most importantly) to ensure the proper delivery to metalloproteins that require zinc for their function. Zinc plays catalytic roles in enzymes from all six classes (oxidoreductases, transferases, hydrolases, lyases, isomerases and ligases), being mostly present in hydrolases. The key factor in the biochemical action of zinc resides is its role as Lewis acid by three main mechanisms: (1) activating a water ligand for deprotonation thus leading to formation of a hydroxide (a potent nucleophile) at neutral pH, (2) polarizing the enzyme substrate or (3) stabilizing negatively charged reaction intermediates. This simple role is tuned according to the specific physiological requirements by the zinc ligands and by a hydrogen bond network (outer sphere ligands) in the protein structure.