Active zinc binding sites of zinc metalloenzymes.

Abstract

The participation of zinc in widely diversified biological reactions focuses attention on its chemistry. A number of its properties relate to its biological utilization and versatility. Its amphoteric properties allow the zinc-coordinated water to exist as a "hydronium" or hydroxide ion even at neutrality. Its coordination sphere is flexible and adapts to a wide variety of ligands, allowing for a multiplicity of types and numbers of coordination complex geometries. Its stable d shell signifies that it is neither oxidized nor reduced; yet it participates in enzymatic oxidoreduction reactions in coordination with an organic cofactor. X-ray crystallographic analyses of twelve zinc enzymes now show that catalytic zinc is bound by three protein ligands, whereas structural zinc atoms are fully coordinated by four ligands. Water is always a ligand to the catalytic zinc while the protein ligands occur in an order of frequency of His >> Glu > Asp = Cys. The zinc-bound water is the critical component of the active site; it is activated for enzymatic catalysis by the identity and arrangement of the ligands coordinated to zinc. Thus, ultimately, it is this water molecule which, upon entering the zinc coordination sphere, is activated either by ionization, polarization or displacement. As a result of the properties of this metal, zinc metalloenzymes and zinc proteins participate in a wide variety of metabolic processes including carbohydrate, lipid, protein and nucleic acid synthesis, regulation and degradation.