Saturation behavior of superoxide dismutation catalyzed by the iron containing superoxide dismutase of E. coli B

Fee, James A.; McClune, Gregory J.; O’Neill, Peter; Fielden, E.M.

doi:10.1016/s0006-291x(81)80107-6

Cited by 40 publications

(27 citation statements)

References 19 publications

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“…Thus where k 4 and k -4 are the rate constants describing the forward and backward rates of the Fe 2+ (H 2 O)‚O 2 •-+ H + S Fe 3+ (OH -) + H 2 O 2 reaction (15,21), with the subscripts mut and opt indicating whether the rate constant in question pertains to a mutant or WT-FeSOD. Assuming that the backward reaction accelerates by a factor similar to that by which the forward reaction decelerates (54) in the case of a low reorganization energy as supported by SOD's rapid turnover and very similar oxidized and reduced state crystal structures (13,55,56), we obtain Thus, a plot of the predicted percent activity retained, as a function of the shift in E m , is provided in Figure 6. On the basis of this highly simplified model, our measured shifts in E m should produce catalytic activities 33% and <5% of that of WT-FeSOD, for Q69H-and Q69E-FeSOD, respectively.…”

Section: Q69h-fesodmentioning

confidence: 98%

The Crucial Importance of Chemistry in the Structure−Function Link: Manipulating Hydrogen Bonding in Iron-Containing Superoxide Dismutase^,

2006

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Fe-containing superoxide dismutase's active site Fe is coordinated by a solvent molecule, whose protonation state is coupled to the Fe oxidation state. Thus, we have proposed that H-bonding between glutamine 69 and this solvent molecule can strongly influence the redox activity of the Fe in superoxide dismutase (SOD). We show here that mutation of this Gln to His subtly alters the active site structure but preserves 30% activity. In contrast, mutation to Glu otherwise preserves the active site structure but inactivates the enzyme. Thus, enzyme function correlates not with atom positions but with residue identity (chemistry), in this case. We observe strong destabilization of the Q69E-FeSOD oxidized state relative to the reduced state and intermediate destabilization of oxidized Q69H-FeSOD. Indeed, redox titrations indicate that mutation of Gln69 to His increases the reduction potential by 240 mV, whereas mutation to Glu appears to increase it by more than 660 mV. We find that this suffices to explain the mutants' loss of activity, although additional factors may also contribute. The strongly elevated reduction potential of Q69E-FeSOD may reflect reorganization of the active site H-bonding network, including possible reversal of the polarity of the key H-bond between residue 69 and coordinated solvent.

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Section: Q69h-fesodmentioning

confidence: 98%

The Crucial Importance of Chemistry in the Structure−Function Link: Manipulating Hydrogen Bonding in Iron-Containing Superoxide Dismutase^,

2006

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“…In this mechanism the inactive inhibitor-bound enzyme is six-coordinated, while the active form remains five-coordinated, with substrate binding causing the displacement of one of the manganese ligands. A third proposed mechanism suggested that the catalytic reaction occurs through an outer sphere mechanism and instead utilizes an alternate anion-binding site in the active site, possibly at the base of the funnel [216–218]. This proposal is based upon various anions inhibiting the activity of FeSOD, but without directly coordinating the metal center.…”

Section: Manganese and Iron Superoxide Dismutasesmentioning

confidence: 99%

The structural biochemistry of the superoxide dismutases

Perry

Shin

Getzoff

et al. 2010

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

438

332

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The discovery of superoxide dismutases (SODs), which convert superoxide radicals to molecular oxygen and hydrogen peroxide, has been termed the most important discovery of modern biology never to win a Nobel Prize. Here, we review the reasons this discovery has been underappreciated, as well as discuss the robust results supporting its premier biological importance and utility for current research. We highlight our understanding of SOD function gained through structural biology analyses, which reveal important hydrogen-bonding schemes and metal-binding motifs. These structural features create remarkable enzymes that promote catalysis at faster than diffusion-limited rates by using electrostatic guidance. These architectures additionally alter the redox potential of the active site metal center to a range suitable for the superoxide disproportionation reaction and protect against inhibition of catalysis by molecules such as phosphate. SOD structures may also control their enzymatic activity through product inhibition; manipulation of these product inhibition levels has the potential to generate therapeutic forms of SOD. Markedly, structural destabilization of the SOD architecture can lead to disease, as mutations in Cu,ZnSOD may result in familial amyotrophic lateral sclerosis, a relatively common, rapidly progressing and fatal neurodegenerative disorder. We describe our current understanding of how these Cu,ZnSOD mutations may lead to aggregation/fibril formation, as a detailed understanding of these mechanisms provides new avenues for the development of therapeutics against this so far untreatable neurodegenerative pathology.

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“…The more extensively studied metalloenzyme, superoxide dismutase (SOD), disproportionates O 2 − to afford H 2 O 2 and O 2 . 204,216 The active site's redox potential and access to protons would be the two most important parameters governing this chemistry. The metal ion of SOR sits at the surface of the protein exposed to solvent.…”

Section: Active Site Structure and Mechanismmentioning

confidence: 99%

Synthetic Analogues of Cysteinate‐Ligated Non‐Heme Iron and Non‐Corrinoid Cobalt Enzymes

Kovacs

2004

ChemInform

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Saturation behavior of superoxide dismutation catalyzed by the iron containing superoxide dismutase of E. coli B

Cited by 40 publications

References 19 publications

The Crucial Importance of Chemistry in the Structure−Function Link: Manipulating Hydrogen Bonding in Iron-Containing Superoxide Dismutase^,

The Crucial Importance of Chemistry in the Structure−Function Link: Manipulating Hydrogen Bonding in Iron-Containing Superoxide Dismutase^,

The structural biochemistry of the superoxide dismutases

Synthetic Analogues of Cysteinate‐Ligated Non‐Heme Iron and Non‐Corrinoid Cobalt Enzymes

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Saturation behavior of superoxide dismutation catalyzed by the iron containing superoxide dismutase of E. coli B

Cited by 40 publications

References 19 publications

The Crucial Importance of Chemistry in the Structure−Function Link: Manipulating Hydrogen Bonding in Iron-Containing Superoxide Dismutase,

The Crucial Importance of Chemistry in the Structure−Function Link: Manipulating Hydrogen Bonding in Iron-Containing Superoxide Dismutase,

The structural biochemistry of the superoxide dismutases

Synthetic Analogues of Cysteinate‐Ligated Non‐Heme Iron and Non‐Corrinoid Cobalt Enzymes

Contact Info

Product

Resources

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The Crucial Importance of Chemistry in the Structure−Function Link: Manipulating Hydrogen Bonding in Iron-Containing Superoxide Dismutase^,

The Crucial Importance of Chemistry in the Structure−Function Link: Manipulating Hydrogen Bonding in Iron-Containing Superoxide Dismutase^,