Manganese active site structure

Mariganese-containing catalases have been isolated from three species of bacteria Lactobacillus plantarum [27], Thermus ihemtophUus [28], and Thermoleophilum album [18]. X-ray crystallographic structure analysis [29] has shown that these catalases contain a dinudear manganese core. During catalysis, the dinudear manganese active site cydes between the Mn"- and Mn2"oxidation states [30]. 

We begin this overview of manganese biochemistry with a brief account of its role in the detoxification of free radicals, before considering the function of a dinuclear Mn(II) active site in the important eukaryotic urea cycle enzyme arginase. We then pass in review a few microbial Mn-containing enzymes involved in intermediary metabolism, and conclude with the very exciting recent results on the structure and function of the catalytic manganese cluster involved in the photosynthetic oxidation of water. 

Figure 38 Structural models of the manganese complex which constitutes the active site responsible for the water oxidation in WOC...

Ring opening of the cryptand derived from condensation of the branched tetraamine tren with 2,6-diacetylpyridine (in a 2 3 molar ratio) in the presence of manganese(II) acetate, NaBF4," " and NEts yielded the dinuclear complex Mn2L(CH3COO)](BF4)3 (where L = XH5) which was proposed as a structural model for active sites in natural systems. The Mn—Mn separation is 4.82 A compared with that of 4.9 A found in the D-xylose isomerase from Streptomyces rubiginosus. 

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,... 

The most common metal encountered in electron transfer systems is iron, although copper and manganese play vital functions. Merely to emphasise the complexity of the catalysts that are used in biology, the structures of the active sites of ascorbate oxidase (Fig. 10-11) and superoxide dismutase (Fig. 10-12) are presented. It is clear that we have only just begun to understand the exact ways in which metal ions are used to control the reactivity of small molecules in biological systems. 

Early proposals suggested [72] that catalase contains a p-oxo-bis(p-carboxylato)-dimanganese core. The UV-Vis spectra of this structural motif present in model complexes exhibit 480-520 nm d-d absorptions [73] similar to the UV-Vis absorption bands of manganese catalases. The EPR studies of oxidized T. ther-mophilus catalase [74] also suggested a MnIIIMnI" p-oxo-bis(p-carboxy 1 ato) core as a possible structural motif for the active site. 

Recently, three TPO models have been reported bis (salicylidene)ethylenediaminato cobalt(II) [Co(salen)] in MeOH (14), cobalt(II)tetraphenylporphyrin (CoTPP) (25) in DMF, and manganese phthalocyanine (Mn-Pc) in DMF (16). These models have been reported as having the TPO-mimic function of oxygenating skatole, a tryptophan analogue, to form 2-formamidoacetophenone (FA). However, one of the most critical problems for these models is the lack of structural similarity between the TPO active site (heme) and these models. The structure of these models is not similar to the heme in TPO with respect to the central metal and/or the ligand. Furthermore, Fe(salen) does not possess the TPO-mimic function (14). 

Carrell et al. (2002) XAS, ESR Manganese complex and cocomplexes in Structure and dynamics of a molecular active site + — + Water splitting... 

The importance of reactions 1-3 in the biosphere is clear. However, relatively little is known about the catalytic mechanisms of these reactions, particularly reactions 2 and 3. In order to better understand the catalytic mechanisms of these enzymes, it is important to establish the correlation between metal site structure and enzymatic function. X-ray absorption spectroscopy is one of the premier tools for determining the local structural environment of metalloprotein metal sites. In the following, we summarize our results using X-ray absorption spectroscopy to characterize the structure of the Mn active site environments in manganese catalase and in the OEC and show how these structural results can be used to deduce details of the catalytic mechanism of these enzymes. 

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