Ligation and Reactivity of Methionine-Oxidized Cytochrome c

• DOI: 10.1021/acs.inorgchem.8b00010
• Publication Date: 2018-04-30T14:46:46Z
• Authors: Fangfang Zhong; Ekaterina V. Plet...
• Keywords: Hemeprotein; Metalloprotein

Met80, one of the heme iron ligands in cytochrome c (cyt c), is readily oxidized to Met sulfoxide (Met-SO) by several biologically relevant oxidants. The modification has been suggested affect both electron-transfer (ET) and apoptotic functions this metalloprotein. coordination Met-oxidized cyt (Met-SO c) critical for these but remained poorly defined. We present electronic absorption, NMR, EPR spectroscopic investigations as well kinetic studies mutational analyses identify yeast iso-1 Met-SO c. Similar alkaline form native c, Lys73 Lys79 ligate ferric Met80-oxidized protein, takes place at much lower pH. ferrous ligated Met-SO, implying redox-linked ligand switch modified protein. Binding with model peptide microperoxidase-8 provide a rationale alterations ligation role polypeptide packing Imidazole binding experiments have revealed that Lys dissociation from K73A/K79G/M80K (M80K#) more than 3 orders magnitude slower opening pocket limits Met80 replacement Lys-to-Met-SO substitution gates ET Co(terpy)22+. Owing slow step, reaction possible, which not case nonswitchable M80A M80K#. Acidic conditions cause water (p Ka = 6.3 ± 0.1), increasing intrinsic peroxidase activity This pH-driven may be mechanism boost function specifically cells.