Superoxide dismutases structural models

Nickel is found in thiolate/sulflde environment in the [NiFe]-hydrogenases and in CODH/ACS.33 In addition, either a mononuclear Ni-thiolate site or a dinuclear cysteine-S bridged structure are assumed plausible for the new class of Ni-containing superoxide dismutases, NiSOD (A).34 [NiFe]-hydrogenase catalyzes the two-electron redox chemistry of dihydrogen. Several crystal structures of [NiFe]-hydrogenases have demonstrated that the active site of the enzyme consists of a heterodinuclear Ni—Fe unit bound to thiolate sulfurs of cysteine residues with a Ni—Fe distance below 3 A (4) 35-39 This heterodinuclear active site has been the target of extensive model studies, which are summarized in Section 6.3.4.12.5. 

Carloni et al.91 applied the DFT(PZ) calculations to investigate the electronic structure of various models of oxydized and reduced Cu, Zn superoxide dismutase. The first stage of the enzymatic reaction involves the electron transfer from Cu" ion to superoxide. The theoretical investigations provided a detailed description of the electronic structure of the molecules involved in the electron transfer process. The effect of charged groups, present in the active center, on the electron transfer process were analyzed and the Argl41 residue was shown to play a crucial role. 

This discussion of copper-containing enzymes has focused on structure and function information for Type I blue copper proteins azurin and plastocyanin, Type III hemocyanin, and Type II superoxide dismutase s structure and mechanism of activity. Information on spectral properties for some metalloproteins and their model compounds has been included in Tables 5.2, 5.3, and 5.7. One model system for Type I copper proteins39 and one for Type II centers40 have been discussed. Many others can be found in the literature. A more complete discussion, including mechanistic detail, about hemocyanin and tyrosinase model systems has been included. Models for the blue copper oxidases laccase and ascorbate oxidases have not been discussed. Students are referred to the references listed in the reference section for discussion of some other model systems. Many more are to be found in literature searches.50... 

Cu,Zn superoxide dismutase. Essentially, these observations support a stepwise one-electron model again. Interestingly, the oxidation state of copper does not change during the catalytic reaction, i.e. the sole kinetic role of the histidine coordinated metal center is to alter the electronic structures of the substrate and 02 in order to facilitate the electron transfer process between them. 

We have already seen a number of models for the zinc(II) containing enzymes such as carbonic anhydrase in Section 11.3.2. Zinc is an essential component in biochemistry, and forms part of the active site of more then 100 enzymes, of which hydrolases (such as alkaline phosphatase and carboxypeptidase A), transferases (e.g. DNA and RNA polymerase), oxidoreductases (e.g. alcohol dehydrogenase and superoxide dismutase) and lysases (carbonic anhydrase) are the most common. In addition, the non-enzyme zinc finger proteins have an important regulatory function. In many of these systems, the non-redox-active Zn2+ ion is present as a Fewis acidic centre at which substrates are coordinated, polarised and hence activated. Other roles of zinc include acting as a template and playing a structural or regulatory role. 

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 ... 

Three Mn catalases have been purified and characterized, and all appear to have similar Mn structures (17). The Mn stoichiometry is ca. 2 Mn/subunit, suggesting a dinuclear Mn site. The optical spectrum of the as-isolated enzyme has a broad weak absorption band at ca. 450-550 nm in addition to the protein absorption at higher energies. This spectrum is similar to those observed for Mn(III) superoxide dismutase and for a variety of Mn(III) model complexes, thus implying that at least some of the Mn in Mn catalase is present as Mn(III). In particular, the absorption maximum at ca. 500 nm is similar in energy and intensity to the transitions seen for oxo-carboxylato-bridged Mn dimers, suggesting that a similar core structure may be seen for Mn catalase (18). 

Mn catalase cycles between the Mn /Mfo and the Mn /Mn oxidation states during catalysis and is thus, in some sense, the two-electron analog of Mn superoxide dismutase. One possible mechanistic model, based on the known coordination chemistry of Mn dimers and the crystal structures of Mn catalase, is shown in Scheme 3. In this scheme, the bridging solvent molecules play a critical role in... 

Another problem with small models is that molecules from the solution (e.g. water) may come in and stabilise tetragonal structures and higher coordination numbers [224]. It is illustrative that very few inorganic con5)lexes reproduce the properties of the blue copper proteins [66,67], whereas typical blue-copper sites have been constructed in several proteins and peptides by metal substitution, e.g. insulin, alcohol dehydrogenase, and superoxide dismutase [66]. This shows that the problem is more related to protection from water and dimer formation than to strain. 

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