Copper-zinc superoxide dismutase water

Manganese can also be a catalyst. Manganese [as Mn(III)] in superoxide dismutase from Thermus thermophilus (Stallings et al., 1984, 1985) is surrounded by three histidines, one aspartate oxygen, and water in a trigonal bipyramidal arrangement. The fifth coordination site is occupied by a water molecule. In copper, zinc-superoxide dismutase (Cu,Zn = SOD), as described later, there are two metals (copper and zinc). Each bonds to and are separated by this same histidine group. 

Starting at the far left, we see a water molecule, two common amino acids, alanine and tryptophan, a segment of a DNA double helix, a segment of a protein single helix, and the folded polypeptide chain of the enzyme copper, zinc superoxide dismutase or SOD. 

The imidazole-bridge dimetallic centre in copper-zinc superoxide dismutase (EC 1.15.1.1) was a novel structural feature that had not previously been encountered in coordination chemistry [151], The Cu(II) ion is co-ordinated by four histidine side chains, His44, His46, His 118 and His61, and there is evidence for a fifth axial water ligand. 

Zinc deficiency places an increased demand on selenium (Se) pools in daphnids. As little as 5.0 p,g Se/L in zinc-free water eliminated overt cuticle damage and substantially increased reproduction, but did not alter the shortened life span. Cladocerans at the threshold of selenium deficiency will become overtly selenium-deficient when zinc supplies are lacking. Insufficient copper introduces cuticle problems in daphnids similar to those introduced by insufficient zinc or selenium, increasing the likelihood of a proposed relation between glutathione peroxidase (which contains selenium), and copper-zinc superoxide dismutase. High levels of dietary tin increased zinc loss from rats. Zinc prevented toxic effects of vanadium (lO.Omg/kg BW) on bone metabolism of weanling rats. 

Water soluble protein with a relative molecular mass of ca. 32600, which particularly contains copper and zinc bound like chelate (ca. 4 gram atoms) and has superoxide-dismutase-activity. It is isolated from bovine liver or from hemolyzed, plasma free erythrocytes obtained from bovine blood. Purification by manyfold fractionated precipitation and solvolyse methods and definitive separation of the residual foreign proteins by denaturizing heating of the orgotein concentrate in buffer solution to ca. 65-70 C and gel filtration and/or dialysis. 

IV. Superoxide dismutase (EC 1.15.1.1) Within a cell the superoxide dismutases (SODs) constitute the first line of defense against ROS. Superoxide radical (02) is produced where an electron transport chain is present, as in mitochondria and chloroplasts, but 02 activation may occur in other subcellular locations such as glyoxysomes, peroxisomes, apoplast and the cytosol. Thus SODs are present in all these cellular locations, converting superoxide into hydrogen peroxide and water (i.e. copper/zinc SODs are typically found in the nuclei and cytosol of eukaryotic cells). 

Cu—Zn superoxide dismutases (SODs) [87,88] are abundant in eukaryotic cells and may serve to protect cells against the toxic effects of superoxide or deleterious oxy-products derived from 02 . The active site copper and zinc ions are 6.3 A apart and are bridged by a histidine imidazolate. In the oxidized form Cu(II) is roughly pentacoordinate, with four His N s and a water molecule. A highly conserved Arg residue is thought to stabilize Cu(II)-bound anions (e.g., Cu(II)—02 ) a redox reaction releases 02, generating Cu(I), which can reduce more 02 substrate to give peroxide and Cu(II). 

There are a number of enzymes that catalyse the dismutation of superoxide in vivo, viz. the superoxide dismutases [50,51], They are metalloproteins which contain copper, zinc, manganese or iron as the prosthetic group. The enzyme catalase exists in vivo to degrade hydrogen peroxide within cells to form water and oxygen [43]. As stated earlier, there are barely detectable amounts of these two enzymes in the synovial fluid of arthritic patients and hence both superoxide radicals and hydrogen peroxide are potential mediators of damage to the biomolecules of the synovial fluid. 

It has been concluded from a study of the optical and e.p.r. spectra of Co —Cu bovine superoxide dismutase, in which zinc has been replaced by cobalt, that the cobalt site reactivity should be described in terms of reaction of the Co-imidazolate-Cu system as a whole the crystal structure reported last year indicated that the metals were linked by a common histidine residue. There is an exchange interaction between the cobalt and copper however, this is abolished when the linking imidazole is protonated. Further evidence for the close proximity and interactive dependence of the zinc and copper binding sites was obtained from a study of the 4 Cu protein a two-fold enhancement of the activity of 2 Cu dismutase was observed upon occupation of the zinc sites by the Cu ". On the basis of C1 n.m.r. studies, Fee and Ward have suggested that one co-ordination position of Cu in superoxide dismutase is normally occupied by water they further suggest that superoxide can displace the solvent to form a cupric peroxide complex. 

The kinetics of formation of the intermediate complex between catalase and HgOa have been re-examined, and reports of pulse radiolysis experiments with superoxide dismutase and its manganese-containing form have appeared. Bovine superoxide dismutase is known to contain two Cu and two Zn atoms per molecule and it has been shown that the copper site, which is directly involved in the catalytic activity, comprises three nitrogens and a water molecule bound to the metal in a field with less than axial symmetry. Less is known of the zinc site but it has recently been shown, by e.p.r. spectroscopy with the cobalt-copper form of the enzyme, that the... 

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