The Zinc proteome: a tale of stability and functionality

Abstract

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.

Helical Shape of Helicobacter pylori Requires an Atypical Glutamine as a Zinc Ligand in the Carboxypeptidase Csd4

“…2, E and F). Two additional density peaks that are best modeled as either water or hydroxide ions (2.2 and 2.3 Å) are also observed (Table 2), together forming an infrequently observed six-coordinate zinc site (33).…”

Macrocyclic Zn(II) Complexes: Synthesis, Structure and Hydrolysis of p-Nitrophenyl Acetate (pNPA)

“…The active sites of these enzymes feature a zinc centre attached to the protein backbone by three or four amino acid residues, the nature of which influences the specific function of the enzyme (Bharathi et al 2013). As one of the most prevalent transition metal cofactors in biological systems, it plays structural, signaling, and regulatory roles and is found in the most classes of the enzymes (most commonly hydrolases) (Andreini et al 2006 andSousa et al 2009). The discovery of its presence as the catalytic centre in the hydrolytic metalloenzyme carbonic anhydrase (CA) (Keilin & Man 1939) was followed by its characterization in carboxypeptidase and soon after in enzymes of all classes (Vallee & Naurath 1954).…”

Trinuclear zinc complexes for biologically relevant μ3-oxoanion binding and carbon dioxide fixation

“…Herein, we report a trinuclear zinc scaffold and its ability to capture biologically relevant m 3 -oxoanions and catalytically convert CO 2 (Fig. 1).…”

“…The zinc cation has key roles in enzymatic activity, structural organization and functional regulation due to its strong Lewis acidity and other unusual chemical properties, including rapid ligand exchange, flexible coordination and lack of redox chemistry under physiological conditions 4 . However, the physical properties of Zn(II) make most spectroscopic techniques and methodologies employed for probing other biological metals inapplicable to the characterization of zinc enzymes 2,4 . Synthetic zinc models have attracted much attention [5][6][7][8][9][10][11] because they are more amenable to structural, spectroscopic and mechanistic studies that could provide information regarding zinc chemistry and its coordination environment 12,13 .…”

“…Z inc is the second most common metallic element in biological systems and the only one known to be essential for functions of enzymes in all six of the fundamental classes [1][2][3] . The zinc cation has key roles in enzymatic activity, structural organization and functional regulation due to its strong Lewis acidity and other unusual chemical properties, including rapid ligand exchange, flexible coordination and lack of redox chemistry under physiological conditions 4 .…”