Cytochrome c peroxidase
| Cytochrome c peroxidase | |||||||||
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ExPASy NiceZyme view | | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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| Cytochrome c peroxidase | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Organism | |||||||
| Symbol | CCP | ||||||
UniProt | P00431 | ||||||
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Cytochrome c peroxidase, or CCP, is a water-soluble heme-containing enzyme of the peroxidase family that takes reducing equivalents from cytochrome c and reduces hydrogen peroxide to water:
- CCP + H2O2 + 2 ferrocytochrome c + 2H+ → CCP + 2H2O + 2 ferricytochrome c
CCP can be derived from aerobically grown yeast strains and can be isolated in both native and recombinant forms with high yield from Saccharomyces cerevisiae. The enzyme’s primary function is to eliminate toxic radical molecules produced by the cell which are harmful to biological systems. It works to maintain low concentration levels of hydrogen peroxide, which is generated by the organism naturally through incomplete oxygen reduction. When glucose levels in fast growing yeast strains are exhausted, the cells turn to respiration which raises the concentration of mitochondrial H2O2.[1] In addition to its peroxidase activity, it acts as a sensor and a signaling molecule to exogenous H2O2, which activates mitochondrial catalase activity.[2] In eukaryotes, CCP contain a mono-b-type haem cofactor and is targeted to the intermembrane space of the mitochondria. In prokaryotes, CCP contains a c-type diheme cofactor and is localized to the periplasm of the cell. Both enzymes work to resist peroxide-induced cellular stress.[3]
CCP plays an integral role in enabling inter-protein biological
Cytochrome c peroxidase can react with
It was first isolated from baker's yeast by R. A. Altschul, Abrams, and Hogness in 1940,[6] though not to purity. The first purified preparation of yeast CCP dates to Takashi Yonetani and his preparation by ion exchange chromatography in the early 1960s. The X-ray structure was the work of Thomas Poulos and coworkers in the late 1970s.[7] CCP is the first heme enzyme to have its structure successfully solved through X-ray crystallography.
The yeast enzyme is a monomer of molecular weight 34,000, containing 293 amino acids, and contains as well a single non-covalently bound
Much like catalase, the reaction of cytochrome c peroxidase proceeds through a three-step process, forming first a Compound I and then a Compound II intermediate:
- CCP + ROOH → Compound I + ROH + H2O
- CCP-compound I + e− + H+ → Compound II
- Compound II + e− + H+ → CCP
CCP in the resting state has a
CCP has high sequence identity to the closely related ascorbate peroxidase enzyme.
Amino acid composition
Amino acid analyzer studies reveal presence of residues of Asp, Thr, Ser, Glu, Pro, Gly, Ala, Val, Met, Ile, Leu, Tyr, Phe, Lys, His, Arg, Cys, and Trp in crystalline CCP. The enzyme shows an unusual amino acid pattern compared to other peroxidase. Plant peroxidase such as horseradish peroxidase and pineapple peroxidase B have low lysine, tryptophan, and tyrosine contents and high cysteine content. In contrast, CCP has high lysine, tryptophan, and tyrosine content and low cysteine content.[10] The enzyme contains a 68-residue sequence at the N-terminus of its monomeric protein, which targets it to the inter-membrane space of the mitochondria where it can the complex with cytochrome c and where it carries out its sensor, signaling and catalytic roles.[1] Studies indicate the distal arginine (Arg48), a highly conserved amino acid among peroxidase, plays an important role in the catalytic activity of CCP by controlling its active site through stabilization of the reactive oxyferryl intermediate from control of its access.[11]
