Ionization of tyrosine and lysine residues in native and modified horse cytochrome <i>c</i>

Boswell, A P; Moore, Geoffrey R.; Williams, R. J. P.; Harris, David; Wallace, C J A; Bocieck, S; Welti, Dieter H.

doi:10.1042/bj2130679

Cited by 14 publications

(8 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pH-dependence of the Ile-57 resonances of tuna ferrocytochrome c is similar both to the temperature-dependence of the Ile-57 resonances of tuna and horse ferrocytochromes (Moore & Williams, 1980c,e) and to the pH-dependence of the Ile-57 5CH3 resonance of horse ferrocytochrome c (Boswell et al, 1983); with increasing pH or temperature, below the denaturation point, the 5CH3 resonance shifts downfield and the y-CH3 resonance shifts upfield. A large increase in linewidth only occurs for the pH-dependence.…”

Section: Ofhorse Cytochrome Csupporting

confidence: 59%

“…A large increase in linewidth only occurs for the pH-dependence. The cause of the pH-induced chemical-shift variation is the ionization of a lysine residue (Boswell et al, 1983 that produced by a variation in temperature: the position of Ile-57 with respect to the surrounding amino acid side chains is perturbed.…”

Section: Ofhorse Cytochrome Cmentioning

confidence: 99%

“…2 and 4), these properties demonstrate that this region of the protein structure is particularly sensitive to the nature of neighbouring amino acid side chains. -This accounts for the perturbations resulting from modification of lysine residues (Boswell et al, 1983), and for the perturbations resulting from cleavage of the Arg-38-Lys-39 peptide bond (D. E. Harris & G. R. Moore, unpublished work). Cleavage of this bond produces a protein with an activity about 50% of that of native cytochrome c in assays with depleted mitochondria (Harris & Offord, 1977).…”

Section: Structure Ofeukaryotic Cytochromes Cmentioning

confidence: 99%

See 2 more Smart Citations

The conformation of eukaryotic cytochrome c around residues 39, 57, 59 and 74

Robinson¹,

Boswell²,

Huang³

et al. 1983

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

1H-n.m.r. studies of horse, tuna, Candida krusei and Saccharomyces cerevisiae cytochromes c showed that each of the proteins contains a similar cluster of residues at the bottom of the protein that assists in shielding the haem from the solvent. The relative positions of the residues forming these clusters vary continuously with temperature, and they change with the change in protein redox state. This conformational heterogeneity is discussed with reference to the conformational flexibility of cytochrome c around residues 57, 59 and 74. Spectroscopic measurements of pKa values for Lys-55 (horse and tuna cytochromes c) and His-33 and His-39 (C. krusei and S. cerevisiae cytochromes c) are in excellent agreement with expectations based on chemical-modification studies of horse cytochrome c. [Bosshard & Zürrer (1980) J. Biol. Chem. 255, 6694-6699] and on the X-ray-crystallographic structure of tuna cytochrome c [Takano & Dickerson (1981) J. Mol. Biol. 153, 79-94, 95-115].

show abstract

Section: Ofhorse Cytochrome Csupporting

confidence: 59%

Section: Ofhorse Cytochrome Cmentioning

confidence: 99%

Section: Structure Ofeukaryotic Cytochromes Cmentioning

confidence: 99%

See 1 more Smart Citation

The conformation of eukaryotic cytochrome c around residues 39, 57, 59 and 74

Robinson¹,

Boswell²,

Huang³

et al. 1983

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

show abstract

“…With the exception of parameters that are directly affected by the pK of basic side-chains, such as binding to ion-exchange resins, there are no significant differences. In contrast, the guanidyl or acetimidyl proteins show small decreases in biological activity and redox potential [8], which in the acetimidyl case, at least, is associated with a minor conformational change [33]. Wallace [7] has shown that this is a consequence of the modification of lysine residue 53, and no other.…”

Section: Resultsmentioning

confidence: 99%

Alkylamine derivatives of cytochrome c

Wallace

Corthésy

1987

European Journal of Biochemistry

View full text Add to dashboard Cite

For investigations of the functional roles of the lysine residues of cytochrome c, analogues in which these residues are modified without charge loss are highly desirable. The 19 lysine residues of the horse heart protein have been modified by reductive alkylation. Two analogues were prepared, using formaldehyde and acetone as the dialkylating and monoalkylating reagent respectively. Modification was shown to be clean and quantitative. Characterisation of the alkylamine derivatives by physicochemical measurements and biological activity determinations was carried out. The potential of these analogues in structure/function studies of cytochrome c is discussed. It is illustrated by their use, in conjunction with other lysine‐modified derivatives, to investigate the extent to which surface charge determines redox potential, and to study the physicochemical changes that accompany rising pH. In the latter case the observed phenomena are not as closely correlated as previously thought, suggesting that there is a complex set of rearrangements of structure underlying the functional changes. The data confirm that modification of the lysine residues influences these changes. These residues participate in numerous surface intramolecular links, so the lack of correlation may be explained if each of the changing parameters were under the influence of a different set of residues. However, neither a lysine residue, nor a histidine residue directly displaces methionine from the sixth coordination position of the haem iron at alkaline pH.

show abstract

“…It has been shown that the alkaline form of cytochrome c is stabilized by chemical modifications of amino acids, cleavage of certain parts of the polypeptide chain, perturbation of interactions inside the heme crevice, interactions with anionic phospholipids, increased temperature, and the presence of denaturants, resulting in a lower pK a (29,41,(67)(68)(69)(70)(71)(72). Such conditions are associated with local or global destabilization of the protein fold induced by the deprotonation of one or more residues.…”

Section: Discussionmentioning

confidence: 99%

Nitration of Solvent-exposed Tyrosine 74 on Cytochrome c Triggers Heme Iron-Methionine 80 Bond Disruption

Abriata

Cassina

Tortora

et al. 2009

Journal of Biological Chemistry

100

135

View full text Add to dashboard Cite

Cytochrome c, a mitochondrial electron transfer protein containing a hexacoordinated heme, is involved in other physiologically relevant events, such as the triggering of apoptosis, and the activation of a peroxidatic activity. The latter occurs secondary to interactions with cardiolipin and/or post-translational modifications, including tyrosine nitration by peroxynitrite and other nitric oxide-derived oxidants. The gain of peroxidatic activity in nitrated cytochrome c has been related to a heme site transition in the physiological pH region, which normally occurs at alkaline pH in the native protein. Herein, we report a spectroscopic characterization of two nitrated variants of horse heart cytochrome c by using optical spectroscopy studies and NMR. Highly pure nitrated cytochrome c species modified at solvent-exposed Tyr-74 or Tyr-97 were generated after treatment with a flux of peroxynitrite, separated, purified by preparative high pressure liquid chromatography, and characterized by mass spectrometry-based peptide mapping. It is shown that nitration of Tyr-74 elicits an early alkaline transition with a pK a ‫؍‬ 7.2, resulting in the displacement of the sixth and axial iron ligand Met-80 and replacement by a weaker Lys ligand to yield an alternative low spin conformation. Based on the study of site-specific Tyr to Phe mutants in the four conserved Tyr residues, we also show that this transition is not due to deprotonation of nitro-Tyr-74, but instead we propose a destabilizing steric effect of the nitro group in the mobile ⍀-loop of cytochrome c, which is transmitted to the iron center via the nearby Tyr-67. The key role of Tyr-67 in promoting the transition through interactions with Met-80 was further substantiated in the Y67F mutant. These results therefore provide new insights into how a remote post-translational modification in cytochrome c such as tyrosine nitration triggers profound structural changes in the heme ligation and microenvironment and impacts in protein function.

show abstract

Ionization of tyrosine and lysine residues in native and modified horse cytochrome c

Cited by 14 publications

References 33 publications

The conformation of eukaryotic cytochrome c around residues 39, 57, 59 and 74

The conformation of eukaryotic cytochrome c around residues 39, 57, 59 and 74

Alkylamine derivatives of cytochrome c

Nitration of Solvent-exposed Tyrosine 74 on Cytochrome c Triggers Heme Iron-Methionine 80 Bond Disruption

Contact Info

Product

Resources

About