The biochemistry and enzymology of zinc enzymes

BAHR, G; TOMATIS PE; VILA AJ

Comprehensive Inorganic Chemistry III;

Elsevier

Lugar: Oxford; Año: 2023; p. 231 - 267

Zn2þ is an essential transition metal ion for the life cycle of all living organisms. This metal ion plays key roles in stabilizingproteins, as a cellular messenger, but it is mostly present as an essential cofactor in enzymes. The intracellular levels of Zn2þare tightly regulated to prevent adventitious zinc binding to other metalloproteins, to limit its toxic effects at highconcentrations, 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 andligases), being mostly present in hydrolases. The key factor in the biochemical action of zinc resides is its role as Lewis acid bythree main mechanisms: (1) activating a water ligand for deprotonation thus leading to formation of a hydroxide (a potentnucleophile) 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 bondnetwork (outer sphere ligands) in the protein structure.