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Cytochrome c peroxidase

August 18, 2023

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:

Cytochrome c peroxidase
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EC no.1.11.1.5
CAS no.9029-53-2
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Cytochrome c peroxidase
Identifiers
OrganismSaccharomyces cerevisiae
SymbolCCP
UniProtP00431
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StructuresSwiss-model
DomainsInterPro
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 electron transfer. The negative charge transfer process is carried out by a complex formed between cytochrome c and cytochrome c peroxidase which occurs in the inter-membrane space of mitochondria. The mechanism involves ferrous cytochrome c (Cc) providing electrons for the Cc-CcP system to reduce hydrogen peroxide to water.[4] The complex is formed by non-covalent interactions.[5]

Cytochrome c peroxidase can react with hydroperoxides other than hydrogen peroxide, but the reaction rate is much slower than with hydrogen peroxide.

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 heme b. It is negatively charged and is a moderately-sized enzyme (34.2 kDa). The apoenzyme, not active and bound to substrates, has an acidic isoelectric point of pH 5.0-5.2.[8] Unusual for proteins, this enzyme crystallizes when dialysed against distilled water. More so, the enzyme purifies as a consequence of crystallization, making cycles of crystallization an effective final purification step.

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-catalyzed redox cycle

CCP in the resting state has a ferric heme, and, after the addition of two oxidizing equivalents from a hydroperoxide (usually hydrogen peroxide), it becomes oxidised to a formal oxidation state of +5 (FeV, commonly referred to as ferryl heme. However, both low-temperature magnetic susceptibility measurements and Mössbauer spectroscopy show that the iron in Compound I of CCP is a +4 ferryl iron, with the second oxidising equivalent existing as a long-lived free-radical on the side-chain of the tryptophan residue (Trp-191).[9] In its resting state, the Fe atom (Fe (III)) in the CCP heme is paramagnetic with high spin (S= 5/2). Once the catalytic cycle is initiated, the iron atom is oxidized to form an oxyferryl intermediate (Fe(IV)=O) has low spin (S= 1/2).[4] This is different from most peroxidases, which have the second oxidising equivalent on the porphyrin instead. Compound I of CCP is fairly long-lived, decaying to CCP-compound II with a half-life at room temperature of 40 minutes to a couple hours.

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]

References

  1. ^ a b Kathiresan M, Martins D, English AM (December 2014). "Respiration triggers heme transfer from cytochrome c peroxidase to catalase in yeast mitochondria". Proceedings of the National Academy of Sciences of the United States of America. 111 (49): 17468–73. Bibcode:2014PNAS..11117468K. doi:10.1073/pnas.1409692111. PMC 4267377. PMID 25422453.
  2. ^ Martins D, Kathiresan M, English AM (December 2013). "Cytochrome c peroxidase is a mitochondrial heme-based H2O2 sensor that modulates antioxidant defense". Free Radical Biology & Medicine. 65: 541–51. doi:10.1016/j.freeradbiomed.2013.06.037. PMID 23831190.
  3. ^ Atack JM, Kelly DJ (2007). "Structure, mechanism and physiological roles of bacterial cytochrome c peroxidases". Advances in Microbial Physiology. 52: 73–106. doi:10.1016/S0065-2911(06)52002-8. ISBN 9780120277520. PMID 17027371.
  4. ^ a b Volkov AN, Nicholls P, Worrall JA (November 2011). "The complex of cytochrome c and cytochrome c peroxidase: the end of the road?". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1807 (11): 1482–503. doi:10.1016/j.bbabio.2011.07.010. PMID 21820401.
  5. ^ Guo M, Bhaskar B, Li H, Barrows TP, Poulos TL (April 2004). "Crystal structure and characterization of a cytochrome c peroxidase-cytochrome c site-specific cross-link". Proceedings of the National Academy of Sciences of the United States of America. 101 (16): 5940–5. Bibcode:2004PNAS..101.5940G. doi:10.1073/pnas.0306708101. PMC 395902. PMID 15071191.
  6. ^ Altchul AM, Abrams R, Hogness TR (1941). "Cytochrome c peroxidase" (PDF). J. Biol. Chem. 136 (3): 777–794. doi:10.1016/S0021-9258(18)73036-6.
  7. ^ Poulos TL, Freer ST, Alden RA, Edwards SL, Skogland U, Takio K, Eriksson B, Xuong N, Yonetani T, Kraut J (January 1980). "The crystal structure of cytochrome c peroxidase" (PDF). The Journal of Biological Chemistry. 255 (2): 575–80. doi:10.1016/S0021-9258(19)86214-2. PMID 6243281.
  8. ^ Yonetani T (1970). "Cytochromec Peroxidase". Cytochrome c peroxidase. Advances in Enzymology and Related Areas of Molecular Biology. Vol. 33. pp. 309–35. doi:10.1002/9780470122785.ch6. ISBN 9780470122785. PMID 4318313.
  9. ^ Sivaraja M, Goodin DB, Smith M, Hoffman BM (August 1989). "Identification by ENDOR of Trp191 as the free-radical site in cytochrome c peroxidase compound ES". Science. 245 (4919): 738–40. Bibcode:1989Sci...245..738S. doi:10.1126/science.2549632. PMID 2549632.
  10. ^ Ellfolk N (1967). "Cytochrome c peroxidase. 3. The amino acid composition of cytochrome c peroxidase of Baker's yeast". Acta Chemica Scandinavica. 21 (10): 2736–42. doi:10.3891/acta.chem.scand.21-2736. PMID 5585683.
  11. ^ Iffland A, Tafelmeyer P, Saudan C, Johnsson K (September 2000). "Directed molecular evolution of cytochrome c peroxidase". Biochemistry. 39 (35): 10790–8. doi:10.1021/bi001121e. PMID 10978164.

External links

  • , maintained by the .
  • The UniProt entry for yeast cytochrome c peroxidase.

August 18, 2023
cytochrome, peroxidase, water, soluble, heme, containing, enzyme, peroxidase, family, that, takes, reducing, equivalents, from, cytochrome, reduces, hydrogen, peroxide, water, identifiersec, 5cas, 9029, 2databasesintenzintenz, viewbrendabrenda, entryexpasynice. 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 Cytochrome c peroxidaseIdentifiersEC no 1 11 1 5CAS no 9029 53 2DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumGene OntologyAmiGO QuickGOSearchPMCarticlesPubMedarticlesNCBIproteinsCytochrome c peroxidaseIdentifiersOrganismSaccharomyces cerevisiaeSymbolCCPUniProtP00431Search forStructuresSwiss modelDomainsInterPro CCP H2O2 2 ferrocytochrome c 2H CCP 2H2O 2 ferricytochrome cCCP 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 electron transfer The negative charge transfer process is carried out by a complex formed between cytochrome c and cytochrome c peroxidase which occurs in the inter membrane space of mitochondria The mechanism involves ferrous cytochrome c Cc providing electrons for the Cc CcP system to reduce hydrogen peroxide to water 4 The complex is formed by non covalent interactions 5 Cytochrome c peroxidase can react with hydroperoxides other than hydrogen peroxide but the reaction rate is much slower than with hydrogen peroxide 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 heme b It is negatively charged and is a moderately sized enzyme 34 2 kDa The apoenzyme not active and bound to substrates has an acidic isoelectric point of pH 5 0 5 2 8 Unusual for proteins this enzyme crystallizes when dialysed against distilled water More so the enzyme purifies as a consequence of crystallization making cycles of crystallization an effective final purification step 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 CCPCCP catalyzed redox cycleCCP in the resting state has a ferric heme and after the addition of two oxidizing equivalents from a hydroperoxide usually hydrogen peroxide it becomes oxidised to a formal oxidation state of 5 FeV commonly referred to as ferryl heme However both low temperature magnetic susceptibility measurements and Mossbauer spectroscopy show that the iron in Compound I of CCP is a 4 ferryl iron with the second oxidising equivalent existing as a long lived free radical on the side chain of the tryptophan residue Trp 191 9 In its resting state the Fe atom Fe III in the CCP heme is paramagnetic with high spin S 5 2 Once the catalytic cycle is initiated the iron atom is oxidized to form an oxyferryl intermediate Fe IV O has low spin S 1 2 4 This is different from most peroxidases which have the second oxidising equivalent on the porphyrin instead Compound I of CCP is fairly long lived decaying to CCP compound II with a half life at room temperature of 40 minutes to a couple hours CCP has high sequence identity to the closely related ascorbate peroxidase enzyme Amino acid composition EditAmino 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 References Edit a b Kathiresan M Martins D English AM December 2014 Respiration triggers heme transfer from cytochrome c peroxidase to catalase in yeast mitochondria Proceedings of the National Academy of Sciences of the United States of America 111 49 17468 73 Bibcode 2014PNAS 11117468K doi 10 1073 pnas 1409692111 PMC 4267377 PMID 25422453 Martins D Kathiresan M English AM December 2013 Cytochrome c peroxidase is a mitochondrial heme based H2O2 sensor that modulates antioxidant defense Free Radical Biology amp Medicine 65 541 51 doi 10 1016 j freeradbiomed 2013 06 037 PMID 23831190 Atack JM Kelly DJ 2007 Structure mechanism and physiological roles of bacterial cytochrome c peroxidases Advances in Microbial Physiology 52 73 106 doi 10 1016 S0065 2911 06 52002 8 ISBN 9780120277520 PMID 17027371 a b Volkov AN Nicholls P Worrall JA November 2011 The complex of cytochrome c and cytochrome c peroxidase the end of the road Biochimica et Biophysica Acta BBA Bioenergetics 1807 11 1482 503 doi 10 1016 j bbabio 2011 07 010 PMID 21820401 Guo M Bhaskar B Li H Barrows TP Poulos TL April 2004 Crystal structure and characterization of a cytochrome c peroxidase cytochrome c site specific cross link Proceedings of the National Academy of Sciences of the United States of America 101 16 5940 5 Bibcode 2004PNAS 101 5940G doi 10 1073 pnas 0306708101 PMC 395902 PMID 15071191 Altchul AM Abrams R Hogness TR 1941 Cytochrome c peroxidase PDF J Biol Chem 136 3 777 794 doi 10 1016 S0021 9258 18 73036 6 Poulos TL Freer ST Alden RA Edwards SL Skogland U Takio K Eriksson B Xuong N Yonetani T Kraut J January 1980 The crystal structure of cytochrome c peroxidase PDF The Journal of Biological Chemistry 255 2 575 80 doi 10 1016 S0021 9258 19 86214 2 PMID 6243281 Yonetani T 1970 Cytochromec Peroxidase Cytochrome c peroxidase Advances in Enzymology and Related Areas of Molecular Biology Vol 33 pp 309 35 doi 10 1002 9780470122785 ch6 ISBN 9780470122785 PMID 4318313 Sivaraja M Goodin DB Smith M Hoffman BM August 1989 Identification by ENDOR of Trp191 as the free radical site in cytochrome c peroxidase compound ES Science 245 4919 738 40 Bibcode 1989Sci 245 738S doi 10 1126 science 2549632 PMID 2549632 Ellfolk N 1967 Cytochrome c peroxidase 3 The amino acid composition of cytochrome c peroxidase of Baker s yeast Acta Chemica Scandinavica 21 10 2736 42 doi 10 3891 acta chem scand 21 2736 PMID 5585683 Iffland A Tafelmeyer P Saudan C Johnsson K September 2000 Directed molecular evolution of cytochrome c peroxidase Biochemistry 39 35 10790 8 doi 10 1021 bi001121e PMID 10978164 External links EditCytochrome c peroxidase maintained by the Kraut Research Group The UniProt entry for yeast cytochrome c peroxidase Portal Biology Retrieved from https en wikipedia org w index php title Cytochrome c peroxidase amp oldid 1146630622, wikipedia, wiki, book, books, library,

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