The (Not Completely Irreversible) Population of a Misfolded State of Cytochrome <i>c</i> under Folding Conditions

Soffer, Jonathan B.; Fradkin, Emma; Pandiscia, Leah; Schweitzer‐Stenner, Reinhard

doi:10.1021/bi301586e

Cited by 13 publications

(21 citation statements)

References 74 publications

(155 reference statements)

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“…Such a quantum mixed state yields low spinlike Raman spectra and a charge transfer band in the region between 620 and 630 nm, as obtained [155]. If the quantum mixed state is pentacoordinated, the Soret absorption peaks between respective low and high spin band positions, again in agreement with our absorption spectra [147]. Figure 24: Resonance Raman spectra of 0.5 mM ferricytochrome c measured at the indicated pH after the protein was subjected to oxidizing conditions at pH 11.5 for 7 days.…”

Section: Oligomerization Of Cytochrome Csupporting

confidence: 89%

“…Their results indeed suggest that such oligomers might be more stable than the native state and that protein are prone to misfolding at mildly unfolding conditions. That is exactly what we obtained [147].…”

supporting

confidence: 88%

“…A rather peculiar strategy for obtaining cytochrome c oligomers with an intact secondary structure was recently reported by us [147]. We oxidized cytochrome c at pH 11.5 (state V) and allowed incubation times up to a week at this condition.…”

Section: Oligomerization Of Cytochrome Cmentioning

confidence: 99%

“…CT2 is assignable to a heme → iron transition in high and quantum mixed heme irons. The spectrum was taken from [147] with permission.…”

Section: Oligomerization Of Cytochrome Cmentioning

confidence: 99%

“…The spectra were taken with 442 nm near -band excitation. The figure was taken from [147] with permission.…”

Section: Oligomerization Of Cytochrome Cmentioning

confidence: 99%

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Cytochrome c: A Multifunctional Protein Combining Conformational Rigidity with Flexibility

Schweitzer‐Stenner

2014

New Journal of Science

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Cytochrome has served as a model system for studying redox reactions, protein folding, and more recently peroxidase activity induced by partial unfolding on membranes. This review illuminates some important aspects of the research on this biomolecule. The first part summarizes the results of structural analyses of its active site. Owing to heme-protein interactions the heme group is subject to both in-plane and out-of-plane deformations. The unfolding of the protein as discussed in detail in the second part of this review can be induced by changes of pH and temperature and most prominently by the addition of denaturing agents. Both the kinetic and thermodynamic folding and unfolding involve intermediate states with regard to all unfolding conditions. If allowed to sit at alkaline pH (11.5) for a week, the protein does not return to its folding state when the solvent is switched back to neutral pH. It rather adopts a misfolded state that is prone to aggregation via domain swapping. On the surface of cardiolipin containing liposomes, the protein can adopt a variety of partially unfolded states. Apparently, ferricytochrome c can perform biological functions even if it is only partially folded.

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Section: Oligomerization Of Cytochrome Csupporting

confidence: 89%

supporting

confidence: 88%

Section: Oligomerization Of Cytochrome Cmentioning

confidence: 99%

“…CT2 is assignable to a heme → iron transition in high and quantum mixed heme irons. The spectrum was taken from [147] with permission.…”

Section: Oligomerization Of Cytochrome Cmentioning

confidence: 99%

“…The spectra were taken with 442 nm near -band excitation. The figure was taken from [147] with permission.…”

Section: Oligomerization Of Cytochrome Cmentioning

confidence: 99%

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Cytochrome c: A Multifunctional Protein Combining Conformational Rigidity with Flexibility

Schweitzer‐Stenner

2014

New Journal of Science

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Ultrafast Heme Dynamics of Ferric Cytochrome c in Different Environments: Electronic, Vibrational, and Conformational Relaxation

Karunakaran

2015

ChemPhysChem

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The excited-state dynamics of ferric cytochrome c (Cyt c), an important electron-transfer heme protein, in acidic to alkaline medium and in its unfolded form are investigated by using femtosecond pump-probe spectroscopy, exciting the heme and Tryptophan (Trp) to understand the electronic, vibrational, and conformational relaxation of the heme. At 390 nm excitation, the electronic relaxation of heme is found to be ≈150 fs at different pH values, increasing to 480 fs in the unfolded form. Multistep vibrational relaxation dynamics of the heme, including fast and slow processes, are observed at pH 7. However, in the unfolded form and at pH 2 and 11, fast phases of vibrational relaxation dominate, revealing the energy dissipation occurring through the covalent bond interaction between the heme and the nearest amino acids. A significant shortening of the excited-state lifetime of Trp is observed at various pH values at 280 nm excitation due to resonance energy transfer to the heme. The longer time constant (25 ps) observed in the unfolded form is attributed to a complete global conformational relaxation of Cyt c.

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Hydrogen bond donation to the heme distal ligand of Staphylococcus aureus IsdG tunes the electronic structure

et al. 2015

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Staphylococcus aureus IsdG catalyzes the final step of staphylococcal iron acquisition from host hemoglobin, whereby host-derived heme is converted to iron and organic products. The Asn7 distal pocket residue is known to be critical for enzyme activity, but the influence of this residue on the substrate electronic structure was unknown prior to this work. Here, an optical spectroscopic and density functional theory characterization of azide- and cyanide-inhibited wild type and N7A IsdG is presented. Magnetic circular dichroism data demonstrate that Asn7 perturbs the electronic structure of azide-inhibited, but not cyanide-inhibited, IsdG. As the iron-ligating α-atom of azide, but not cyanide, can act as a hydrogen bond acceptor, these data indicate that the terminal amide of Asn7 is a hydrogen bond donor to the α-atom of a distal ligand to heme in IsdG. Circular dichroism characterization of azide- and cyanide-inhibited forms of WT and N7A IsdG strongly suggests that the Asn7···N3 hydrogen bond influences the orientation of a distal azide ligand with respect to the heme substrate. Specifically, density functional theory calculations suggest that Asn7···N3 hydrogen bond donation causes the azide ligand to rotate about an axis perpendicular to the porphyrin plane and weakens the π-donor strength of the azide ligand. This lowers the energies of the Fe 3d xz and 3d yz orbitals, mixes Fe 3d xy and porphyrin a 2u character into the singly-occupied molecular orbital, and results in spin delocalization onto the heme meso carbons. These discoveries have important implications for the mechanism of heme oxygenation catalyzed by IsdG.

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The (Not Completely Irreversible) Population of a Misfolded State of Cytochrome c under Folding Conditions

Cited by 13 publications

References 74 publications

Cytochrome c: A Multifunctional Protein Combining Conformational Rigidity with Flexibility

Cytochrome c: A Multifunctional Protein Combining Conformational Rigidity with Flexibility

Ultrafast Heme Dynamics of Ferric Cytochrome c in Different Environments: Electronic, Vibrational, and Conformational Relaxation

Hydrogen bond donation to the heme distal ligand of Staphylococcus aureus IsdG tunes the electronic structure

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