Superoxide dismutase catalytic mechanism

Strangely, these small molecules are also used industrially as oxidation catalysts, however, small changes in their structures lead to dramatically different behaviour. In these model compounds, unlike SOD2, the metal is bound by two oxygen and two nitrogen atoms in a square planar orientation with axial positions occupied by water or reactive oxygen species. The superoxide dismutase catalytic cycle has been proposed to occur by a one electron mechanism ... 

M.E. Me Adam, E.M. Fielden, F. Favelle, F. Calabrese, D. Cocco, and G. Rotilio, The involvement of the bridging imidazolate in the catalytic mechanism of action of bovine superoxide dismutase. 

Pick M, Rabani J, Yost F, Fridovich I (1974) The catalytic mechanism of the manganese-containing superoxide dismutase of Escherichia coli studied by pulse radiolysis. J Am Chem Soc 96 7329-7333... 

Korsvik et al. reported ceria NPs used as catalysts mimicking superoxide dismutase (SOD) (Korsvik et al., 2007). The polycrystalline 3-5 nm sized ceria NPs show excellent catalytic rate constant even exceeding that of enzyme SOD. The mechanism should be further elucidated. 

LaveUe F, McAdam ME, Fielden EM, Roberts PB. (1977) A pulse-radiolysis study of the catalytic mechanism of the iron-containing superoxide dismutase from Photobacterium leio nathi. Riochem J 6 3-11. 

Fig. 27. The catalytic mechanism of Cu, Zn-superoxide dismutase Oj displaces the axial water molecule of Cu2+ reducing it to Cu+. Protonation of the Cu02 complex liberates 02 and dissolves the ligand bond between His61 and copper. A second -Oj binds to copper, oxidizing it to Cu2+. Protonation produces H202, whereas deprotonation of His61 reestablishes the Cu-His61 bond, releasing H202. From Getzoff et al. 1983 [229] with permission...

The mechanisms by which manganese complexes and manganese superoxide dismutase react with superoxide radicals are of interest as knowledge of the kinetic parameters and the reaction pathways may allow the synthesis of model compounds with specific chemical features. These compounds may then have clinical application or may allow the control of specific redox chemistry in catalytic processes. 

Forman and Fridovich (1973) using an indirect assay whereby O2 was generated either by the action of xanthine oxidase on xanthine or by the mechanical infusion of potassium superoxide in tetrahydrofuran. The generated OJ was allowed to react with ferricytochrome c or with tetra-nitromethane and the product formation was monitored spectroscopically. Details of the two assays are given in Section 11.3. Addition of superoxide dismutase inhibits the formation of products. A rate constant of 2 X 10 M sec was determined for all three enzymes. This value agreed with the rate constant determined by pulse radiolysis for the copper/zinc enzyme (Klug-Roth et al., 1973 Fielden et al., 1974). The mechanism of action of the superoxide dismutases has been investigated by the technique of pulse radiolysis which is described in Section II.2. The bovine erythrocyte copper/zinc enzyme is the most studied form as far as the molecular and catalytic properties are concerned (Rotilio and Fielden,... 

The generation of O2 from potassium superoxide was also applied to stop-flow procedures. In this method O2 was dissolved in dimethyl sulfoxide and stabilized in 18-crown-6-polyether. This method is useful for mechanistic studies indeed, McClune and Fee (1976) were able to obtain catalytic rate constants for bovine copper/zinc superoxide dismutase as a function of pH in various buffers. More recently the mechanism of catalysis and of anion inhibition of iron superoxide dismutase from E. coli have been examined by this method using a specially constructed stop-flow spectrophotometer (Bull and Fee, 1985). A limitation of the method is that the pre-equilibrium state cannot be properly investigated because of the time resolution of the stop-flow equipment (== 5 msec). 

Fig. 12. Schematic drawing of the catalytic mechanism of CujZojSuperoxide dismutase. The superoxide displaces the axial water molecule at the Cu II) and reduces the copper to Cu(I). Concomitantly the bond from Cu to His 61 is broken and Oj is released. The Cu-facing nitrogen of His 61 becomes protonated and a second becomes bound. An electron is transferred from Cu(I), coupled with a proton transfer from His 61. After additon of a second proton from an active-site water, the uncharged hydrogen peroxide is rctosed. (With permission from Ref.

How to determine protonation modes in reaction centers of enzymes is a very important issue in biochemistry [1-8], The protonation is obviously related to the catalytic activities of active side chains of amino residues the protonation and deprotonation to side chains of charged acids such as Glu, Asp, Arg, Lys, and His yield Brpnsted-Lowry acids and bases, catalyzing various chemical reactions. Also in metalloenzymes and these model systems, protonations are often critical parts of the reaction mechanisms. For instance, in (1) the water-oxidizing center (WOC) in photosystem II [9-14], (2) the Mn dimeric center in catalase [15-21], and (3) the Mn center in Mn superoxide dismutases (MnSODs)[22,23], the following reactions proceed, respectively ... 

Figure 4 shows proposed catalytic mechanisms for superoxide dismutases (SOD) and superoxide reductases (SOR) [37, 38]. A single redox metal is present at all these enzyme active sites, oscillating between two oxidation states +2 and -i-3 for Fe, Ni, or Mn, H-1 and +2 for Cu). 

In addition, Zn can be part of heterodinuclear active sites such as CuZn superoxide dismutase, an enzyme that has been discussed in the Cu section. Here, we will describe the active site structure and, whenever possible, the postulated catalytic mechanism of representative members of the enzyme classes mentioned above. We will also address some very recent structural results concerning other less weU-studied Zn-enzymes. 

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