Effect on intrinsic peroxidase activity of substituting coevolved residues from Ω-loop C of human cytochrome c into yeast iso-1-cytochrome c.

ABSTRACT: Naturally-occurring variants of human cytochrome c (Cytc) that induce thrombocytopenia IV occur within Ω-loop C (residues 40-57). These variants enhance the peroxidase activity of human Cytc apparently by facilitating access to the heme by destabilizing Ω-loops C and D (residues 70-85). Given the importance of peroxidase activity in the early stages of apoptosis, we identified three sites with the EVmutation algorithm in or near Ω-loop C that coevolve and differ between yeast iso-1-Cytc and human Cytc. We prepared iso-1-Cytc variants with all possible combinations of the S40T, V57I and N63T substitutions to determine if these residues decrease the peroxidase activity of iso-1-Cytc to that of human Cytc producing an effective off state for a peroxidase signaling switch. At pH 6 and above, a

SUBMITTER: Frederick AK 

PROVIDER: S-EPMC9162143 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature