The Zinc proteome: a tale of stability and functionality.

Zinc proteins constitute a very important portion of the large number of Metalloproteins currently known. However, contrary to what happens with biological systems containing Fe(II), Fe(III), Cu(II), Mn(II), Mn(III), Ni(II), Co(III) or other commonly found biologically relevant metal cofactors, the particular chemical properties of the Zn(II) ion mean that only a very small number of experimental techniques can be directly applied in the study of the metal coordination spheres present in Zinc proteins. The information obtainable from publicly available structural databases such as the Protein Data Bank can therefore be of particularly high significance to a better understanding of these proteins. In this study, we draw a detailed statistical portrait of the Zinc proteome by analysing the metal coordination spheres of the large number of X-ray crystallographic structures of Zinc proteins currently available on the Protein Data Bank. This data is further complemented with quantum mechanical calculations on the most common Zinc coordination spheres to evaluate the intrinsic thermodynamic stability of the several combinations of ligands on a generic and non-specific enzymatic environment, and with molecular electrostatic potential maps. These results provide useful insights into this difficult to characterize but very important Zn-containing subset of the proteome.