The complex of cytochrome c and cytochrome c peroxidase: The end of the road?

Abstract

Cytochrome c (Cc) and cytochrome c peroxidase (CcP) form a physiological complex in the inter-membrane space of yeast mitochondria, where CcP reduces hydrogen peroxide to water using the electrons provided by ferrous Cc. The Cc-CcP system has been a popular choice of study of interprotein biological electron transfer (ET) and in understanding dynamics within a protein-protein complex. In this review we have charted seven decades of research beginning with the discovery of CcP and leading to the latest functional and structural work, which has clarified the mechanism of the intermolecular ET, addressed the putative functional role of a low-affinity binding site, and identified lowly-populated intermediates on the energy landscape of complex formation. Despite the remarkable attention bestowed on this complex, a number of outstanding issues remain to be settled on the way to a complete understanding of Cc-CcP interaction.

LC-MS/MS suggests that hole hopping in cytochrome c peroxidase protects its heme from oxidative modification by excess H2O2

“…Thus, Ccp1 is endowed with a high capacity for hole hopping within its polypeptide, which must be pertinent to its physiological function. In vitro , Ccp1 efficiently couples the two-electron reduction of H 2 O 2 to the one-electron oxidation of two ferrocytochrome c (Cyc II ) molecules: 8 Ccp1 III + H 2 O 2 → CpdI(Fe IV , W191˙ + ) + H 2 O CpdI(Fe IV , W191˙ + ) + Cyc II → CpdII(Fe IV ) + Cyc III CpdII(Fe IV ) + Cyc II + 2H + → Ccp1 III + Cyc III + H 2 O …”

The Metabolic Status Drives Acclimation of Iron Deficiency Responses in Chlamydomonas reinhardtii as Revealed by Proteomics Based Hierarchical Clustering and Reverse Genetics

“…The oxidoreductase domain may connect TBA1 activity to the redox poise of the stroma and implicate a regulation similar to CYN37. The mitochondrial cytochrome c peroxidase (CCPR1) is located at the intermembrane space, reduces hydrogen peroxide to water using the electrons provided by cytochrome c and is thereby involved in scavenging of reactive oxygen species in the mitochondria (96). The mitochondrial thioredoxin o (TRXo) that is found in the same cluster is another player in this scavenging system.…”

Enzymatic Mechanism of Leishmania major Peroxidase and the Critical Role of Specific Ionic Interactions

“…CcP was the first heme peroxidase crystal structure to be determined 1 and thus has played a crucial role in furthering our understanding of structure–function relationships in heme proteins, as well as in elucidating the fundamental mechanisms of interprotein electron transfer (ET). 2 One property that has made enzymes like CcP attractive for detailed biophysical studies is that many heme peroxidases form distinct intermediates that are spectroscopically identifiable and relatively stable. This has allowed most of the intermediates in the generally accepted yeast CcP mechanism to be characterized: $$\mathrm{normalCcP}false({\mathrm{Fe}}^{3+};\mathrm{normalTrp}false)+{\mathrm{H}}_2{\mathrm{O}}_2\to \mathrm{normalCpdI}false({\mathrm{Fe}}^{4+}=\mathrm{normalO};{\mathrm{Trp}}^{+•}false)+{\mathrm{H}}_2\mathrm{normalO}$$ $$\mathrm{normalCpdI}false({\mathrm{Fe}}^{4+}=\mathrm{normalO};{\mathrm{Trp}}^{+•}false)+\mathrm{normalyCytc}false({\mathrm{Fe}}^{2+}false)\to \mathrm{normalCpdII}false({\mathrm{Fe}}^{4+}=\mathrm{normalO};\mathrm{normalTrp}false)+\mathrm{normalyCytc}false({\mathrm{Fe}}^{3+}false)$$ $$\mathrm{normalCpdII}false({\mathrm{Fe}}^{4+}=\mathrm{normalO};\mathrm{normalTrp}false)+{\mathrm{H}}^{+}\rightleftharpoons \mathrm{normalCpdII}false({\mathrm{Fe}}^{3+}-\mathrm{normalOH};{\mathrm{Trp}}^{+•}false)$$ $$\mathrm{normalCpdII}false({\mathrm{Fe}}^{3+}-\mathrm{normalOH};{\mathrm{Trp}}^{+•}false)+\mathrm{normalyCytc}false({\mathrm{Fe}}^{2+}false)+{\mathrm{H}}^{+}\to \mathrm{normalCcP}false({\mathrm{Fe}}^{3+};\mathrm{normalTrp}false)+\mathrm{normalyCytc}false({\mathrm{Fe}}^{3+}false)+{\mathrm{H}}_2\mathrm{normalO}$$…”