Short and long spacer sequences and other structural features of zinc binding sites in zinc enzymes

Abstract

The crystal structures of eleven zinc enzymes have served to identify common features of their Zn binding sites. Two of them have non-catalytic Zn sites, both of which contain four cysteine ligands closely spaced in the linear sequence of the protein with no bound water. In contrast, all the catalytic Zn sites have three protein ligands and, in addition, one coordinated, ‘activated’ water. Histidine is the predominant ligand. The spacing between the first two ligands (1–3 amino acids), the short spacer, ensures a nucleus for Zn binding. The third ligand, separated by from ~20 to ~ 120 amino acids, the long spacer, not only completes the coordination but also aligns protein residues for interaction with the substrate. The short and long spacing observed for catalytic zinc sites may also pertain to Fe and Cu proteins. Metalloenzyme; Metalloproteinase; Zinc; Amino acid spacer sequence