Novel Insights into the Basis for Escherichia coli Superoxide Dismutase's Metal Ion Specificity from Mn-Substituted FeSOD and Its Very High Em

Vance, Carrie K.; Miller, Anne‐Frances

doi:10.1021/bi0113317

Cited by 130 publications

(154 citation statements)

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“…By analogy, it would thus be anticipated that two substrate molecules could simultaneously bind to the active site under turnover conditions. 4,5,[58][59][60][61][62][63] However, other evidence suggests that only one azide can actually bind to the Fe 3+ center in Fe 3+ SOD. First, a single azide ligand (Fe-N(azide) bond length of 2.12 Å) is observed in the X-ray crystal structure of N 3 −Fe 3+ SOD (Figure 1, right), even though a high concentration of azide (100 mM NaN 3 ) was used in the corresponding mother liquor solution.…”

Section: Discussionmentioning

confidence: 99%

“…70 Consequently, neither in FeSOD nor in MnSOD does azide actually displace any of the original active-site ligands, which implies that (i) the coordinated solvent and the Asp ligand are likely to play a crucial role in tuning the redox potential of the active site metal ion in the key reaction intermediates and (ii) a single substrate molecule can coordinate to the metal ion under turnover conditions. 4,5,[58][59][60][61][62][63] …”

Section: Implications For Pink N 3 −Fe 3+ Sod Speciesmentioning

confidence: 99%

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Synthesis, X-Ray Crystallographic Characterization, and Electronic Structure Studies of a Di-Azide Iron(III) Complex: Implications for the Azide Adducts of Iron(III) Superoxide Dismutase

et al. 2008

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We have synthesized and characterized, using X-ray crystallographic, spectroscopic, and computational techniques, a six-coordinate diazide Fe 3+ complex, LFe(N 3 ) 2 (where L is the tetradentate ligand 7-diisopropyl-1,4,7-triazacyclononane-1-acetic acid), that serves as a model of the azide adducts of Fe 3+ superoxide dismutase (Fe 3+ SOD). While previous spectroscopic studies revealed that two distinct azide-bound Fe 3+ SOD species can be obtained at cryogenic temperatures depending on protein and azide concentrations, the number of azide ligands coordinated to the Fe 3+ ion in each species has been the subject of some controversy. In the case of LFe(N 3 ) 2 , the electronic absorption and magnetic circular dichroism spectra are dominated by two broad features centered at 21 500 cm −1 (ε ≈ 4000 M −1 cm −1 ) and ~30 300 cm −1 (ε ≈ 7400 M −1 cm −1 ) attributed to N 3 − → Fe 3+ charge transfer (CT) transitions. A normal coordinate analysis of resonance Raman (RR) data obtained for LFe(N 3 ) 2 indicates that the vibrational features at 363 and 403 cm −1 correspond to the Fe-N 3 stretching modes (ν Fe-N3 ) associated with the two different azide ligands and yields Fe-N 3 force constants of 1.170 and 1.275 mdyne/Å, respectively. RR excitation profile data obtained with laser excitation between 16 000 and 22 000 cm −1 reveal that the ν Fe-N3 modes at 363 and 403 cm −1 are preferentially enhanced upon excitation in resonance with the N 3 − → Fe 3+ CT transitions at lower and higher energies, respectively. Consistent with this result, density functional theory electronic structure calculations predict a larger stabilization of the molecular orbitals of the more strongly bound azide due to increased σ-symmetry orbital overlap with the Fe 3d orbitals, thus yielding higher N 3 − → Fe 3+ CT transition energies. Comparison of our data obtained for LFe(N 3 ) 2 with those reported previously for the two azide adducts of Fe 3+ SOD provides compelling evidence that a single azide is coordinated to the Fe 3+ center in each protein species.© 2008 American Chemical Society * Author to whom correspondence should be addressed. brunold@chem.wisc.edu. Supporting Information Available: Cartesian coordinates of crystal-structure and DFT geometry-optimized LFe(N 3 ) 2 models, INDO/S-CI calculated ZFS parameters for all models of LFe(N 3 ) 2 , DFT predicted MO energies and compositions for LFe(N 3 ) 2 models, TD-DFT calculated electronic excitation energies, Abs and MCD data of LFe(N 3 ) 2 collected at 4.5 K, and analysis of VTVH MCD data collected at 20 661 cm −1 . This material is available free of charge via the Internet at

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Section: Discussionmentioning

confidence: 99%

Section: Implications For Pink N 3 −Fe 3+ Sod Speciesmentioning

confidence: 99%

Synthesis, X-Ray Crystallographic Characterization, and Electronic Structure Studies of a Di-Azide Iron(III) Complex: Implications for the Azide Adducts of Iron(III) Superoxide Dismutase

et al. 2008

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“…The redox potential of all superoxide dismutases was found to be similar, independently of the type of the metal in the active site. It is around midway (ϩ360 mV versus NHE) 1 (17) between the potential for the oxidation (Ϫ160 mV versus NHE) and for the reduction of O 2 .…”

mentioning

confidence: 98%

“…Thus it allows equal driving force (hence k ox ϭ k red ϭ ϳ2 ϫ 10 9 M Ϫ1 s Ϫ1 ) for both half-reactions of the catalytic cycles (Reactions 1 and 2) (18 -20 the E1 ⁄2 is ϩ223 mV versus NHE at pH 7.4, and for Mn-SOD from the Bacillus stearothermophilus and E. coli the E1 ⁄2 were ϩ260 and ϩ310 mV versus NHE at pH 7 (1,21,22). However, when manganese was replaced by iron in the active site of Mn-SOD the enzymatic activity was lost (18), which has been attributed to the decrease of the redox potential below that required for the oxidation of superoxide ion (3,18).…”

mentioning

confidence: 99%

“…The Mn(III) porphyrin, Mn III TE-2-PyP 5ϩ (AEOL-10113) has been shown (23)(24)(25)(26)(27) to possess high SOD-like activity in vitro 1 The abbreviations used are: NHE, normal hydrogen electrode; SOD, superoxide dismutase; meso, refers to the substituents at the 5, 10, 15, and 20 (meso carbon) position of the porphyrin core; ␤, refers to the substituents at ␤-pyrrolic carbons; Mn III T-2-PyP ϩ , Mn(III) 5,10,-15,20-tetrakis(2-pyridyl)porphyrin; Mn III TE-2-PyP 5ϩ (Mn-2E 5ϩ ) (AEOL-10113), manganese(III) 5,10,15,20- with log k cat ϭ 7.76. The compound has further proven effective in protection of SOD-deficient E. coli (26) and in stroke (28,29), spinal cord injury (30,31), diabetes (32,33), sickle cell disease (34), and radiation/cancer (35-38) rodent models of oxidative stress injuries.…”

mentioning

confidence: 99%

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Electrostatic Contribution in the Catalysis of O 2·_Dismutation by Superoxide Dismutase Mimics

Spasojević

Batinić‐Haberle

Rebouças

et al. 2003

Journal of Biological Chemistry

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The Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)-porphyrin (Mn III TE-2-PyP 5؉ ) is a potent superoxide dismutase (SOD) mimic in vitro and was beneficial in rodent models of oxidative stress pathologies. Its high activity has been ascribed to both the favorable redox potential of its metal center and to the electrostatic facilitation assured by the four positive charges encircling the metal center. (ϩ890 mV versus NHE). Thus it allows equal driving force (hence k ox ϭ k red ϭ ϳ2 ϫ 10 9 M Ϫ1 s Ϫ1 ) for both half-reactions of the catalytic cycles (Reactions 1 and 2) (18 -20). For Escherichia coli Fe-SOD,the E1 ⁄2 is ϩ223 mV versus NHE at pH 7.4, and for Mn-SOD from the Bacillus stearothermophilus and E. coli the E1 ⁄2 were ϩ260 and ϩ310 mV versus NHE at pH 7 (1, 21, 22). However, when manganese was replaced by iron in the active site of Mn-SOD the enzymatic activity was lost (18), which has been attributed to the decrease of the redox potential below that required for the oxidation of superoxide ion (3, 18). Such metal ion specificity (2) has been recently explained by the higher affinity of Fe 3ϩ than Mn 3ϩ for hydroxide (6, 8).The crystal structures of different SODs reveal a highly conserved electrostatic "funnel" (13,14,16) that is believed to guide the negatively charged superoxide toward the active site of the enzyme. In the past there have been considerable efforts to evaluate the extent of electrostatic facilitation, but a major difficulty lies in the inability to specifically modify the positively charged residues without affecting the structural integrity of the active site (9).The Mn(III) porphyrin, Mn III TE-2-PyP 5ϩ (AEOL-10113) has been shown (23-27) to possess high SOD-like activity in vitro * This work was supported in part by Grant BA1-0103-1 from the Christopher Reeve Paralysis Foundation and by Aeolus/Incara Pharmaceuticals, Research Triangle Park, NC. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.§ To whom correspondence should be addressed. 1 The abbreviations used are: NHE, normal hydrogen electrode; SOD, superoxide dismutase; meso, refers to the substituents at the 5, 10, 15, and 20 (meso carbon) position of the porphyrin core; ␤, refers to the substituents at ␤-pyrrolic carbons; Mn III T-2-PyP ϩ , Mn(III) 5,10,-15,20-tetrakis(2-pyridyl)porphyrin; Mn III TE-2-PyP 5ϩ (Mn-2E 5ϩ ) (AEOL-10113), manganese(III) 5,10,15,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin; Mn III TM-2(3,4)-PyP 5ϩ (Mn-2(3,4)M 5ϩ ), manganese(III) 5,10,15,20-tetrakis(N-methylpyridinium-2(3,4)-yl)porphyrin, where 2 (AEOL-10112), 3, and 4 refer to ortho, meta, and para isomers, respectively; Mn III Br 8 T-2-PyP ϩ (Mn-Br 8 ϩ ), Mn(III) 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(2-pyridyl)porphyrin; Mn II Br 8 TM-4-PyP 4ϩ , Mn(II) 2,3,7,8,12,13,17,10,15,porphyrin; Mn II Cl 5 TE-2-PyP 4ϩ , Mn(II) ␤-pentachloro-5,10,15,20-tetrakis(N-ethylpyridi...

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Iron Proteins with Mononuclear Active Sites

Emerson¹,

Mehn²,

Que³

2005

Encyclopedia of Inorganic Chemistry

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Metalloenzymes containing a mononuclear nonheme iron center are often involved in dioxygen metabolism. We have divided this superfamily of enzymes into seven subcategories: iron superoxide dismutase and superoxide reductase, lipoxygenase, catechol dioxygenases, α‐keto acid‐dependent enzymes, isopenicillin N synthase, pterin‐dependent hydroxylases, and Rieske dioxygenases. The degree of catalytic versatility and coordination flexibility encompassed by these enzymes is unsurpassed by any other known metalloenzyme superfamily. Herein we discuss the present state of knowledge regarding their active site structures and the critical role the metal center plays in their respective catalytic mechanisms.

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Novel Insights into the Basis for Escherichia coli Superoxide Dismutase's Metal Ion Specificity from Mn-Substituted FeSOD and Its Very High E_m

Cited by 130 publications

References 47 publications

Synthesis, X-Ray Crystallographic Characterization, and Electronic Structure Studies of a Di-Azide Iron(III) Complex: Implications for the Azide Adducts of Iron(III) Superoxide Dismutase

Synthesis, X-Ray Crystallographic Characterization, and Electronic Structure Studies of a Di-Azide Iron(III) Complex: Implications for the Azide Adducts of Iron(III) Superoxide Dismutase

Electrostatic Contribution in the Catalysis of O 2·_Dismutation by Superoxide Dismutase Mimics

Iron Proteins with Mononuclear Active Sites

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