Superoxide dismutase liganding

Imidazoles are of interest as bridging ligands particularly with regard to mimics of the active site of Cu-Zn superoxide dismutase (SOD). Structures with imidazolate bridges have been... 

One last class of mononuclear non-haem iron enzyme that we have not yet considered, consists of the microbial superoxide dismutases with Fe(III) at their active site. The crystal structure of the E. coli enzyme shows a coordination geometry reminiscent of protocatechuate 3,4-dioxygenase, with four endogenous protein ligands, three His and one Asp residue, and one bound water molecule (Carlioz et ah, 1988). 

The transfer of a quadridentate N2S2-donor ligand from M2+ (M = Cr, Mn, Fe, Co or Ni) to Cu2+ (271), already mentioned in Section V.A.l, has a formal connection with an investigation of the mechanism of copper delivery to metalloproteins, such as copper zinc superoxide dismutase. Both are ligand exchange reactions of the type ML + CuL ML + CuL (300). 

The chelate effect in proteins is also important, since the three-dimensional (3-D) structure of the protein can impose particular coordination geometry on the metal ion. This determines the ligands available for coordination, their stereochemistry and the local environment, through local hydrophobicity/hydrophilicity, hydrogen bonding by nearby residues with bound and non-bound residues in the metal ion s coordination sphere, etc. A good example is illustrated by the Zn2+-binding site of Cu/Zn superoxide dismutase, which has an affinity for Zn2+, such that the non-metallated protein can extract Zn2+ from solution into the site and can displace Cu2+ from the Zn2+ site when the di-Cu2+ protein is treated with excess Zn2+. 

It was clear for some time that a number of zinc enzymes required two or more metal ions for full activity, but in the absence of X-ray structural data the location of these metal centres with regard to one another was often uncertain. When the first 3-D structures began to appear, it became clear that the metals were in close proximity. A particular feature of many of these enzymes was the presence of a bridging ligand between two of the metal sites, usually an Asp residue of the protein, which is occasionally replaced by a water molecule. While some of the sites contain only Zn ions, several contain Zn in combination with Cu (in cytosolic superoxide dismutases) Fe (in purple acid phosphatases) or Mg (in alkaline phosphatase and the aminopeptidase of lens). 

These systems are also described as normal copper proteins due to their conventional ESR features. In the oxidized state, their color is light blue (almost undetectable) due to weak d-d transitions of the single Cu ion. The coordination sphere around Cu, which has either square planar or distorted tetrahedral geometry, contains four ligands with N and/or 0 donor atoms [ 12, 22]. Representative examples of proteins with this active site structure (see Fig. 1) and their respective catalytic function include galactose oxidase (1) (oxidation of primary alcohols) [23,24], phenylalanine hydroxylase (hydroxy-lation of aromatic substrates) [25,26], dopamine- 6-hydroxylase (C-Hbond activation of benzylic substrates) [27] and CuZn superoxide dismutase (disproportionation of 02 superoxide anion) [28,29]. 

Sulfur ligands, 633-655 coordination ability, 516 Sulfur monoxide metal complexes instability, 636 Superoxide dismutase, 773 copper complexes, 772 Superoxo complexes, 315-330 binuclear, 323, 325 reactions, 330 bridged... 

Fig. 6.8. H NMR spectra of C112C02 (A) [28] and Cu2Ni2 (B) [29] superoxide dismutase. The dashed lines relate signals belonging to the various histidine ligands of the copper domain. The black-shaded signals disappear when the spectra are recorded in D2O.

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