Manganese superoxide dismutase active site

CL Eisher, J-L Chen, J Li, D Bashford, L Noodleman. Density-functional and electrostatic calculations for a model of a manganese superoxide dismutase active site in aqueous solution. J Phys Chem 100 13498-13505, 1996. 

While the stoichiometries of the Mn SOD enzymes appear to vary, the properties of the Mn-binding site do not. This is borne out in the electronic spectra of these proteins, which display a great degree of similarity despite the diversity of sources from which they have been isolated (Table II). This type of spectrum is distinctive for manganese in the trivalent oxidation state (3). The native enzymes are EPR silent, as might be anticipated if they contained Mn solely as the trivalent ion (S = 2) (1, 6,12,18-20, 24). However, when the enzymes are denatured, the characteristic six-line pattern of Mn(II) (I = 5/2) appears. Magnetic susceptibility studies with the E. coli SOD were consistent with the presence of a monomeric Mn(III) complex with a zero-field splitting of 1 to 2 cm-1 (4). The enzymes are additionally metal specific (however, see Refs. 36 and 37) metal reconstitution studies with E. coli and B. stearothermophilus revealed a strict requirement for Mn for superoxide dismutase activity (2, 22, 23). 

Y. Hsieh, Y. Guan, C. Tu, P.J. Bratt, A. Angerhofer, J.R. Lepock, M.J. Hickey, J.A. Tainer, H.S. Nick, and D.N. Silverman. 1998. Probing the active site of human manganese superoxide dismutase The role of glutamine 143 Biochemistry 37 4731-4739. (PubMed)... 

Manganese superoxide dismutase (MnSOD) is a redox-active manganese enzyme that employs a mononuclear manganese ion at its active site. Discovered in 1970 (52), this enzyme catalyzes the dismuta-tion of superoxide (H02), to dioxygen and hydrogen peroxide, as shown in Scheme 2. Superoxide is the radical, one-electron-reduced... 

Fig. 3. Structure of the active site of manganese superoxide dismutase, based on (76).

A relatively large number of theoretical studies on the complete calculation of redox potentials of transition metal active sites in metalloproteins have been published. Metalloproteins studied include manganese superoxide dismutase, iron superoxide dismutase, copper-zinc superoxide dismutase, iron-sulfur proteins, cytochrome f, components of the photosynthetic reaction center, and peroxidases. ... 

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. 

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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