Chemistry of the imidazolate-bridged bimetallic center in the copper-zinc superoxide dismutase and its model compounds

Abstract

Ligand-bridged polymetallic centers occur in numerous metalloproteins where they perform electron transfer, oxygen transport, and catalytic redox functions.1 The properties of a variety of proteins containing such centers are given in Table I.2-10 One of the most extensively studied members of this group, and probably the best understood, is the Cu-Zn superoxide dismutase (SOD+).Superoxide dismutases are a ubiquitous group of enzymes. Procaryotes and mitochondria of eucaryotic cells have ironor manganese-containing superoxide dismutases while a copper-and zinc-containing superoxide dismutase is found in the cytosol of eucaryotic cells.11-13 These enzymes are believed to protect cells from the toxic effects of superoxide ion, or some product derived from it, by catalyzing the dismutation reaction given in eq 1. Hydrogen peroxide formed in this re-202-+ 2H+ = 02 + H202(1) action is destroyed in vivo, for example, by catalase.Bovine erythrocyte SOD has a molecular weight of 31200 and is composed of two identical subunits.1415 Each subunit contains an active site having one copper and one zinc atom. The X-ray crystal structure at 3-A resolution has been published,2 and coordinates from 2-A data are available.16 As shown in Figure 1, the copper is coordinated to four imidazole nitrogen atoms from histidines-44, -46, -61, and -118 while the zinc is coordinated to histidines-61, -69, and -78 and the carboxylate group of aspartic acid-81. The most interesting and still unique feature of the active site structure is the imidazolate bridge between the two metal ions. The pyrrole hydrogen of the imidazole group of histidine-61 has been removed, allowing for coordination of both copper and zinc. The geometry aground the zinc is approximately tetrahedral, and the four protein ligands to the copper are distorted square planar. Proton NMR data indicate that a water molecule is coordinated to

Electrostatic Basis of Enzyme Catalysis

“…Strothkamp and Lippard, 1982). It was suggested that reduction of the copper is accompanied by displacement and protonation of the bridging imidazolate side chain.…”

Factorial design analysis of the catalytic activity of di‐imine copper(II) complexes in the decomposition of hydrogen peroxide

“…Particularly, interest in imidazole-containing complexes is credited to the large number of active sites in copper proteins where this group is observed [5]. Except for the copper(I)-thioneins, all the copper proteins studied so far exhibited imidazole residues of histidine bounded to the metal center, especially those related to molecular oxygen transport, or activation [6].…”

Mimics of copper proteins: structural and functional aspects

“…In many copper proteins and enzymes, the imidazole ring is an essential metal binding site, and thus a wide variety of imidazole containing ligands have been investigated to mimic structural features of these biomolecules (Strothkamp & Lippard 1982). In our case, some dinuclear copper complexes with a tridentate diimine ligand, in addition to an imidazole as the bridging ligand, were prepared, characterized, and had their catalytic properties investigated.…”