Manganese enzyme function

M.S. Lah, M.M. Dixon, K.A. Pattridge, W.C. Stallings, J.A. Fee, and M.L. Ludwig, Structure-function in Escherichia coli iron superoxide dismutase comparisons with the manganese enzyme from Thermus thermophilus. Biochemistry. 34, 1646-1660 (1995). 

Manganese is an essential metal cofactor in enzymes that coyer the entire range of enzyme functionality. It is only possible to include some of the more important and better-characterized... 

Catalases catalyze the conversion of hydrogen peroxide to dioxygen and water. Two families of catalases are known, one having a heme cofactor and the second a structurally distinct family, found in thermophilic and lactic acid bacteria. The manganese enzymes contain a binuclear active site and the functional form of the enzyme cycles between the (Mn )2 and the (Mn )2 oxidation states. When isolated, the enzyme is in a mixture of oxidation states including the Mn /Mn superoxidized state and this form of the enzyme has been extensively studied using XAS, UV-visible, EPR, and ESEEM spectroscopies. Multifrequency EPR and microwave polarization studies of the (Mn )2 catalytically active enzyme from L. plantarum have also been reported. ... 

Crystal structures of manganese catalases (in the (111)2 oxidation state) from Lactobacillus plantarum,its azide-inhibited complex, " and from Thermus thermophilus have been determined. There are differences between the structures that may reflect distinct biological functions for the two enzymes, the L. plantarum enzyme functions only as a catalase, while the T. thermo-philus enzyme may function as a catalase/peroxidase. The active sites are conserved in the two enzymes and are shown schematically in Figure 32. Each subunit contains an Mu2 active site,... 

Schramm, V. L., and Wedler, F. C, eds. (1986) Manganese in Metabolism and Enzyme Function, Academic Press, Orlando, Florida... 

Some elements are essential to the composition or function of the body. Since the body is mostly water, hydrogen and oxygen are obviously essential elements. Carbon (C) is a component of all life molecules, including proteins, lipids, and carbohydrates. Nitrogen (N) is in all proteins. The other essential nonmetals are phosphorus (P), sulfur (S), chlorine (Cl), selenium (Se), fluorine (F), and iodine (I). The latter two are among the essential trace elements that are required in only small quantities, particularly as constituents of enzymes or as cofactors (nonprotein species essential for enzyme function). The metals present in macro amounts in the body are sodium (Na), potassium (K), and calcium (Ca). Essential trace elements are chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), magnesium (Mg), molybdenum (Mo), nickel (Ni), and perhaps more elements that have not yet been established as essential. 

In the recent years, our work on the PS-II reaction center has mainly involved EPR spectroscopy, to identify and understand the functional properties of the secondary acceptors, essentially two quinones QA and QB interacting with a Fe2+ iron, and of the manganese enzyme which realizes the oxidative cleavage of water (see e.g. Beijer and Rutherford, 1987 or Styring and Rutherford, 1987). The recent development of a method permitting to simply isolate a PS-II reaction center core (Nanba and Satoh, 1987) allowed us to study the primary radical-pair (P-680+, I ). We first worked in collaboration with the Japanese group, then developed our own preparation (Hansson et al., 1987 Frank et al., 1987 Takahashi et al., 1987) and also collaborated with the group of Professor Barber (London, UK). 

Dismukes, G.C. (1986) in Manganese in Metabolism and Enzyme Function, in press. 

Low-molecular-weight catalysts which mimic a natural enzymic function syn-Zymes) have potential utility for the treatment of diseases characterized by the overproduction of a potentially deleterious metabolic by-product or foreign gene product. The discovery and development of pentaaza macrocyclic ligand complexes of manganese(II) as functional mimics of superoxide dismutase (SOD) enzymes and their potential utility as human pharmaceutical agents is described. 

Finally, with the acknowledged similarities that currently exist between several manganese enzymes and counterparts utilizing other metal ions, it seems quite likely that other redox-active manganese enzymes will be discovered in the future. The discussions of data gathering on enzyme systems and model chemistry, both structural and functional, as presented in this article will provide a foundation for exploring current and as yet undiscovered manganese enzymes. 

Much Is known about the enzyme functions of manganese in living organisms from studies in animals and bacteria and about the co-ordination chemistry of manganese with ligands found in biological systems. These aspects have been reviewed by Keen et al. (1984) and Sawyer (1978). 

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