Structural and Functional Models of the Dimanganese Catalase Enzymes. 2. Structure, Electrochemical, Redox, and EPR Properties

Pessiki, Peter J.; Khangulov, Sergei V.; Ho, Douglas M.; Dismukes, G. Charles

doi:10.1021/ja00082a008

Cited by 101 publications

(95 citation statements)

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“…4. Relative to carboxylate ligands, histidine ligands stabilize the reduced Mn(II) oxidation state in complexes [46] and proteins [47,48] and thus may provide a high thermodynamic barrier to oxidation of the Mn 2 (II,II) state in arginase. Also, carboxylate bridges stabilize the reduced Mn(II) state compared to m-OH P bridges in dimanganese complexes [46].…”

Section: Discussionmentioning

confidence: 99%

Catalysis on dinuclear Mn(II) centers: hydrolytic and redox activities of rat liver arginase

et al. 1997

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Rat liver arginase contains a dinuclear Mn 2 (II,II) center in each subunit having EPR properties similar to those observed in Mn-catalases. The principal physiologic role of arginase is catalyzing the hydrolytic cleavage of L-arginine to produce L-ornithine and urea. Here we demonstrate that arginase catalyzes the disproportionation of hydrogen peroxide by a redox mechanism analogous to Mn-catalases, but at rates that are 10 P5 to 10 P6 of k cat for the Mn-catalases, and also exhibits peroxidase activity. The dinuclear Mn 2 (II,II) center is essential for maximal catalase activity, since both the H101N and H126N mutant arginases containing only one Mn(II)/subunit have catalase activities that are ~3% of that for the wild-type enzyme. Like the Mn-catalases, the catalase activity of arginase is not inhibited by millimolar concentrations of CN P , the most potent inhibitor of heme catalases, or by EDTA, a chelator of free metal ions. The catalase activity of arginase is not significantly inhibited by Cl P or F P , in contrast to Mn-catalases, while potent inhibitors of the hydrolytic activity are also effective inhibitors of the catalase activity. These results suggest that lower affinity of hydrogen peroxide to the active site of arginase contributes to the lower catalase activity. EPR spectroscopy reveals that potent inhibitors of the hydrolytic reaction, including N v -hydroxy-L-arginine, Llysine, and L-valine, decouple the electronic interaction between the Mn 2c ions, most probably by removing a m-bridging ligand or by increasing the intermanganese separation. The capacity for arginase to deliver a hydroxide ion to hydrolyze the L-arginine substrate is suggested to arise from a "dinuclear effect", wherein the two metal ions contribute more or less equivalently in deprotonation of metal-bound water molecule. Structure-reactivity analyses of these reactions will provide insights into the factors that control redox versus hydrolytic function in dimanganese clusters. Key words Arginase 7 Manganoenzymes 7 Catalase 7 PeroxidaseAbbreviations CAPS 3-(cyclohexylamino)-1-propanesulfonic acid 7 CAPSO 3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid 7 EPR electron paramagnetic resonance 7 ENDOR electron-nuclear double resonance 7 EXAFS extended X-ray absorption fine structure 7 HEPES N-(2-hydroxyethyl)-piperazine-Nb-(2-ethanesulfonic acid) 7 MES 2-(N-morpholino)ethanesulfonic acid 7 TRIS tris(hydroxymethyl)-aminomethane 7 ZFS zero-field splitting

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Section: Discussionmentioning

confidence: 99%

Catalysis on dinuclear Mn(II) centers: hydrolytic and redox activities of rat liver arginase

et al. 1997

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“…Thus, the coordination sphere of one manganese ion is different from that in manganese complex 1, which can be explained by packing effects and is also known from studies on similar complexes. [34] The two manganese(II) ions, the alkoxide oxygen, and the three atoms of the carboxylate group form a sixmembered ring with a boat conformation, in which O(1), Mn(2), O(2), and C (48) (2) angle is 116.71(12)°. While the nitro group is essentially coplanar with the phenyl ring, the latter is tilted relative to the carboxylate group by 24.8°.…”

Section: Crystal and Molecular Structure Of [Zn 2 (L Npr )-(O 2 Cphnimentioning

confidence: 99%

Nitronyl Nitroxide Radicals Linked to Exchange‐Coupled Metal Dimers – Studies Using X‐ray Crystallography, Magnetic Susceptibility Measurements, EPR Spectroscopy, and DFT Calculations

et al. 2009

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“…The stability of the mixed-valent state depends on the degree of electronic coupling of the two metal ions [9] and, for uncoupled metal ions, a direct two-electron redox transition at a single electrochemical potential is expected. It has been stressed recently that for dimanganese(II) species to achieve a high efficiency of catalase-like activity, formation of the mixedvalence Mn II ϪMn III state must be disfavored.…”

Section: Introductionmentioning

confidence: 99%

A Novel Dimanganese(II) Complex with Two Chloride Bridges − A Two-Electron Oxidation System

Romero

Collomb

Deronzier

et al. 2001

Eur. J. Inorg. Chem.

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Structural and Functional Models of the Dimanganese Catalase Enzymes. 2. Structure, Electrochemical, Redox, and EPR Properties

Cited by 101 publications

References 0 publications

Catalysis on dinuclear Mn(II) centers: hydrolytic and redox activities of rat liver arginase

Catalysis on dinuclear Mn(II) centers: hydrolytic and redox activities of rat liver arginase

Nitronyl Nitroxide Radicals Linked to Exchange‐Coupled Metal Dimers – Studies Using X‐ray Crystallography, Magnetic Susceptibility Measurements, EPR Spectroscopy, and DFT Calculations

A Novel Dimanganese(II) Complex with Two Chloride Bridges − A Two-Electron Oxidation System

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