Probing the Role of Protein Environment in Compound I Formation of Chloroperoxidase (CPO)

2000 ◽  
Vol 122 (15) ◽  
pp. 3599-3605 ◽  
Author(s):  
Marta Filizola ◽  
Gilda H. Loew
Keyword(s):  
Compound I ◽  
Protein Environment

Activation of cytochrome c to a peroxidase compound I-type intermediate by H2O2: relevance to redox signalling in apoptosis

2004 ◽  
Vol 71 ◽  
pp. 97-106 ◽  
Author(s):  
Mark Burkitt ◽  
Clare Jones ◽  
Andrew Lawrence ◽  
Peter Wardman
Keyword(s):  
Cytochrome C ◽  
Hydroxyl Radical ◽  
Redox Regulation ◽  
Chemotherapeutic Agents ◽  
Tyrosyl Radical ◽  
Compound I ◽  
Definitive Evidence ◽  
Enhanced Production ◽  
Physico Chemical

The release of cytochrome c from mitochondria during apoptosis results in the enhanced production of superoxide radicals, which are converted to H2O2 by Mn-superoxide dismutase. We have been concerned with the role of cytochrome c/H2O2 in the induction of oxidative stress during apoptosis. Our initial studies showed that cytochrome c is a potent catalyst of 2′,7′-dichlorofluorescin oxidation, thereby explaining the increased rate of production of the fluorophore 2′,7′-dichlorofluorescein in apoptotic cells. Although it has been speculated that the oxidizing species may be a ferryl-haem intermediate, no definitive evidence for the formation of such a species has been reported. Alternatively, it is possible that the hydroxyl radical may be generated, as seen in the reaction of certain iron chelates with H2O2. By examining the effects of radical scavengers on 2′,7′-dichlorofluorescin oxidation by cytochrome c/H2O2, together with complementary EPR studies, we have demonstrated that the hydroxyl radical is not generated. Our findings point, instead, to the formation of a peroxidase compound I species, with one oxidizing equivalent present as an oxo-ferryl haem intermediate and the other as the tyrosyl radical identified by Barr and colleagues [Barr, Gunther, Deterding, Tomer and Mason (1996) J. Biol. Chem. 271, 15498-15503]. Studies with spin traps indicated that the oxo-ferryl haem is the active oxidant. These findings provide a physico-chemical basis for the redox changes that occur during apoptosis. Excessive changes (possibly catalysed by cytochrome c) may have implications for the redox regulation of cell death, including the sensitivity of tumour cells to chemotherapeutic agents.

The role of distal tryptophan in the bifunctional activity of catalase-peroxidases

2001 ◽  
Vol 29 (2) ◽  
pp. 99-105 ◽  
Author(s):  
G. Regelsberger ◽  
C. Jakopitsch ◽  
P. G. Furtmüller ◽  
F. Rueker ◽  
J. Switala ◽  
...  
Keyword(s):  
Catalase Activity ◽  
Intermediate Compound ◽  
Stopped Flow ◽  
Wild Type ◽  
Compound I ◽  
Wild Type Enzyme ◽  
Catalase Peroxidase ◽  
Electron Reduction ◽  
The One

Catalase-peroxidases are bifunctional peroxidases exhibiting an overwhelming catalase activity and a substantial peroxidase activity. Here we present a kinetic study of the formation and reduction of the key intermediate compound I by probing the role of the conserved tryptophan at the distal haem cavity site. Two wild-type proteins and three mutants of Synechocystis catalase-peroxidase (W122A and W122F) and Escherichia coli catalase-peroxidase (W105F) have been investigated by steady-state and stopped-flow spectroscopy. W122F and W122A completely lost their catalase activity whereas in W105F the catalase activity was reduced by a factor of about 5000. However, the mutations did not influence both formation of compound I and its reduction by peroxidase substrates. It was demonstrated unequivocally that the rate of compound I reduction by pyrogallol or o-dianisidine sometimes even exceeded that of the wild-type enzyme. This study demonstrates that the indole ring of distal Trp in catalase-peroxidases is essential for the two-electron reduction of compound I by hydrogen peroxide but not for compound I formation or for peroxidase reactivity (i.e. the one-electron reduction of compound I).

On the Role of Water in Peroxidase Catalysis: A Theoretical Investigation of HRP Compound I Formation

2010 ◽  
Vol 114 (15) ◽  
pp. 5161-5169 ◽  
Author(s):  
Pietro Vidossich ◽  
Giacomo Fiorin ◽  
Mercedes Alfonso-Prieto ◽  
Etienne Derat ◽  
Sason Shaik ◽  
...  
Keyword(s):  
Theoretical Investigation ◽  
Compound I

scholarly journals Mechanism of 17α,20-Lyase and New Hydroxylation Reactions of Human Cytochrome P450 17A1

2016 ◽  
Vol 291 (33) ◽  
pp. 17143-17164 ◽  
Author(s):  
Francis K. Yoshimoto ◽  
Eric Gonzalez ◽  
Richard J. Auchus ◽  
F. Peter Guengerich
Keyword(s):  
Acetic Acid ◽  
Cytochrome P450 ◽  
Bond Cleavage ◽  
Active Species ◽  
Sterol Biosynthesis ◽  
Compound I ◽  
Human Cytochrome ◽  
Acetyl Radical

Cytochrome P450 (P450) reactions can involve C–C bond cleavage, and several of these are critical in steroid and sterol biosynthesis. The mechanisms of P450s 11A1, 17A1, 19A1, and 51A1 have been controversial, in the context of the role of ferric peroxide (FeO2−) versus perferryl (FeO3+, compound I) chemistry. We reinvestigated the 17α-hydroxyprogesterone and 17α-hydroxypregnenolone 17α,20-lyase reactions of human P450 17A1 and found incorporation of one 18O atom (from 18O2) into acetic acid, consonant with proposals for a ferric peroxide mechanism (Akhtar, M., Lee-Robichaud, P., Akhtar, M. E., and Wright, J. N. (1997) J. Steroid Biochem. Mol. Biol. 61, 127–132; Akhtar, M., Wright, J. N., and Lee-Robichaud, P. (2011) J. Steroid Biochem. Mol. Biol. 125, 2–12). However, the reactions were supported by iodosylbenzene (a precursor of the FeO3+ species) but not by H2O2. We propose three mechanisms that can involve the FeO3+ entity and that explain the 18O label in the acetic acid, two involving the intermediacy of an acetyl radical and one a steroid 17,20-dioxetane. P450 17A1 was found to perform 16-hydroxylation reactions on its 17α-hydroxylated products to yield 16,17α-dihydroxypregnenolone and progesterone, suggesting the presence of an active perferryloxo active species of P450 17A1 when its lyase substrate is bound. The 6β-hydroxylation of 16α,17α-dihydroxyprogesterone and the oxidation of both 16α,17α-dihydroxyprogesterone and 16α,17α-dihydroxypregnenolone to 16-hydroxy lyase products were also observed. We provide evidence for the contribution of a compound I mechanism, although contribution of a ferric peroxide pathway in the 17α,20-lyase reaction cannot be excluded.

The role of H2O2 generation in perfused rat liver and the reaction of catalase compound I and hydrogen donors

1973 ◽  
Vol 154 (1) ◽  
pp. 117-131 ◽  
Author(s):  
Nozomu Oshino ◽  
Britton Chance ◽  
Helmut Sies ◽  
Theodor Bücher
Keyword(s):  
Rat Liver ◽  
Perfused Rat Liver ◽  
Compound I ◽  
Hydrogen Donors ◽  
H2o2 Generation

Supramolecular interaction-induced assemblies of polyanions and 2-aminopyridinium in two polyoxometalate-based hybrids

2018 ◽  
Vol 74 (11) ◽  
pp. 1325-1333 ◽  
Author(s):  
Fengxue Duan ◽  
Xiaoting Liu ◽  
Wei Xu ◽  
Yanchun Tao ◽  
Bao Li ◽  
...  
Keyword(s):  
Hydrogen Bonds ◽  
Electrostatic Interactions ◽  
Functional Materials ◽  
Magnetic Behaviour ◽  
Organic Cations ◽  
Supramolecular Network ◽  
Compound I ◽  
Compound Ii ◽  
Inorganic Components

Organic–inorganic hybrids consisting of organic cations and polyanions are promising functional materials due to their various compositions and structures. An important aspect of these materials is the interactions between the organic and inorganic components, which not only produce the final structures, but also influence the properties. Here, we investigated the interactions between organic cations and polyanions using protonated 2-aminopyridinium (Hap) as the cation, and successfully obtained two polyoxometalate-based hybrids, namely (C5H7N2)4[Mo8O26], (I), and (C5H7N2)2[NiMo6O16(OH)2{CH3C(CH2O)3}2]·4H2O, (II). In the crystal structure of (I), every Hap cation links with two polyanions by donating one or two N—H...O hydrogen bonds, and every polyanion is surrounded by eight Hap cations via terminal or bridging O atoms. Conversely, in compound (II), every Hap cation only links with one polyanion decorated by a triol ligand; this organic–inorganic component further assembles via uncoordinated water molecules. In the extended structures, Hap plays a key role, not only providing a counter charge, but also acting as `glue' linking polyanions in the role of hydrogen-bond donors. In both compounds, as the nodes of the supramolecular network, the polyanions exhibit an ordered two-dimensional arrangement due to strong hydrogen bonds and electrostatic interactions between the organic and inorganic parts. The electrochemistry of compound (I) shows that redox sourcing from polyanions is a surface-controlled process. Conversely, the magnetic behaviour of compound (II) indicates dominant antiferromagnetic properties.

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