Spectroscopic and functional properties of human cytochrome c and its Tyr67 residue mutants (i.e., Tyr67His and Tyr67Arg) have been investigated. In the case of the Tyr67His mutant, we have observed only a very limited structural alteration of the heme pocket and of the Ω-loop involving, among others, the residue Met80 and its bond with the heme iron. Conversely, in the Tyr67Arg mutant the Fe-Met80 bond is cleaved; consequently, a much more extensive structural alteration of the Ω-loop can be envisaged. The structural, and thus the functional modifications, of the Tyr67Arg mutant are present in both the ferric [Fe(III)] and the ferrous [Fe(II)] forms, indicating that the structural changes are independent of the heme iron oxidation state, depending instead on the type of substituting residue. Furthermore, a significant peroxidase activity is evident for the Tyr67Arg mutant, highlighting the role of Arg as a basic, positively charged residue at pH7.0, located in the heme distal pocket, which may act as an acid to cleave the O-O bond in H2O2. As a whole, our results indicate that a delicate equilibrium is associated with the spatial arrangement of the Ω-loop. Clearly, Arg, but not His, is able to stabilize and polarize the negative charge on the Fe(III)-OOH complex during the formation of Compound I, with important consequences on cytochrome peroxidation activity and its role in the apoptotic process, which is somewhat different in yeast and mammals.
Tognaccini, L., Ciaccio, C., D'Oria, V., Cervelli, M., Howes, B.d., Coletta, M., et al. (2016). Structure-function relationships in human cytochrome c: The role of tyrosine 67. JOURNAL OF INORGANIC BIOCHEMISTRY, 155, 56-66.
|Tipologia:||Articolo su rivista|
|Citazione:||Tognaccini, L., Ciaccio, C., D'Oria, V., Cervelli, M., Howes, B.d., Coletta, M., et al. (2016). Structure-function relationships in human cytochrome c: The role of tyrosine 67. JOURNAL OF INORGANIC BIOCHEMISTRY, 155, 56-66.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore BIO/10|
|Revisione (peer review):||Esperti anonimi|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.jinorgbio.2015.11.011|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||feb-2016|
|Titolo:||Structure-function relationships in human cytochrome c: The role of tyrosine 67|
|Autori:||Tognaccini, L; Ciaccio, C; D'Oria, V; Cervelli, M; Howes, Bd; Coletta, M; Mariottini, P; Smulevich, G; Fiorucci, L|
|Appare nelle tipologie:||01 - Articolo su rivista|