Reversible formation of high-valent-iron-oxo porphyrin intermediates in heme-based catalysis: revisiting the kinetic model for horseradish peroxidase

Haandel, M.J.H. van; Primus, Jean-Louis; Teunis, C.J.; Boersma, Marelle G.; Osman, Azizah; Veeger, C.; Rietjens, Ivonne M.C.M.

doi:10.1016/s0020-1693(97)06111-2

Cited by 27 publications

(12 citation statements)

References 38 publications

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“…Based on the rate of compound II formation (k 2 ) and turnover number for Cld, we compute a first-order rate constant for the recombination (k r ) of Ϸ10 7 s Ϫ1 . Moreover, both of these rates far exceed the rate of water/ compound I oxygen-atom exchange observed for horseradish peroxidase (Ͼ1.7 s Ϫ1 ) (23). The data are therefore consistent with the above mechanism, although decomposition of chlorite in a single, concerted step from a metal-bound chlorite cannot be ruled out.…”

Section: Discussionsupporting

confidence: 77%

Mechanism of and exquisite selectivity for O–O bond formation by the heme-dependent chlorite dismutase

Lee

Streit

Zdilla

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

157

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Section: Discussionsupporting

confidence: 77%

Mechanism of and exquisite selectivity for O–O bond formation by the heme-dependent chlorite dismutase

Lee

Streit

Zdilla

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

157

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“…The questions that must be answered in determining a common mechanism for the reactions of the present study include which heme intermediate (hydro)peroxo-iron or oxenoid-iron, catalyses such different conversions, and whether the reactions are electrophilic or nucleophilic. Oxygen exchange studies with horseradish peroxidase, MP-8 and cytochrome P450 showed [12,17,18] that a (hydro)peroxide intermediate is formed prior to oxenoid-iron formation, a conclusion substantiated by rapid kinetic studies with the horseradish peroxidase mutant R38L [19].…”

Section: Discussionmentioning

confidence: 98%

Heme‐(hydro)peroxide mediated O‐ and N‐dealkylation

Boersma¹,

Primus

Koerts

et al. 2000

European Journal of Biochemistry

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The mechanism of microperoxidase-8 (MP-8) mediated O-and N-dealkylation was investigated. In the absence of ascorbate (peroxidase mode), many unidentified polymeric products are formed and the extent of substrate degradation correlates (r 0.94) with the calculated substrate ionization potential, reflecting the formation of radical intermediates.In the presence of ascorbate (P450 mode) formation of polymeric products is largely prevented but, surprisingly, dealkylation is not affected. In addition, aromatic hydroxylation and oxidative dehalogenation is observed. The results exclude a radical mechanism and indicate the involvement of a (hydro)peroxo-iron heme intermediate in P450-type of heteroatom dealkylation.

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“…This 896 Da (ϩ16 Da) Fig. 4 identified the 781-Da (ϩ30 Da) fragment as modified WDRFK (43)(44)(45)(46)(47) and the 896-Da (ϩ16 Da) fragment as EKWDRF (41)(42)(43)(44)(45)(46). A number of product ions were detected by MALDI-TOF MS/MS for the 781-and 896-Da peaks using post-source decay, which could be assigned to the b and y ion systems (predicted by Sherpa lite 4.0.)…”

Section: Uv-visible Spectroscopy Of Mb Wdi-mentioning

confidence: 92%

Monooxygenation of an Aromatic Ring by F43W/H64D/V68I Myoglobin Mutant and Hydrogen Peroxide

Pfister¹,

Ohki²,

Ueno³

et al. 2005

Journal of Biological Chemistry

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Myoglobin (Mb)1 is a small (17 kDa), well characterized heme protein that is often used as a model system for other heme proteins and the reactions they catalyze. In addition to its native function as an oxygen carrier, Mb has been engineered to efficiently perform peroxidase, catalase, and peroxygenase (sulfoxidation and epoxidation) activities (1-4). Scheme 1 shows three major alternate pathways for the reaction with peroxide. The latest novel function to be proposed for Mb is cytochrome P450-type aromatic carbon hydroxylation. Although hydroxylation by P450s has been extensively studied (5-7), the mechanism is still not fully understood (6,8). Input from new model systems could provide additional insight. P450 enzymes capture their substrates near the heme via specific interactions (9 -11), which Mb cannot do. A Trp was, thus, engineered in the heme pocket of Mb to model P450 hydroxylation of aromatic compounds ( Fig. 1) (12, 13). The monooxygenation product has not previously been observed or isolated due to rapid subsequent oxidation steps.The mechanism of hydroxylation by P450s is proving to be quite complex and may even vary among various P450s (7). Some of the proposed mechanisms involve 1) an epoxide intermediate for the aromatic hydroxylation, 2) a concerted direct insertion of oxygen, 3) a non-concerted sequential insertion involving hydrogen abstraction and oxygen rebound, or 4) a more simple non-concerted radical mechanism (6 -8, 14). Recently it has been found that these mechanisms may not be entirely valid, and the actual mechanism may involve two electrophilic oxidants and/or two spin states of the iron oxo species (6,8,14). Although P450cam has been shown to lose its hydroxylation activity when an imidizole is substituted for the axial thiolate ligand (15, 16), in contrast, chloroperoxidase retains its chlorination, peroxidation, epoxidation, and catalase activities when its thiolate ligand is mutated to histidine (17). Also, studies with iron porphyrin compounds have demonstrated that imidazole ligation can replace the thiolate in P450 type reactions under certain conditions (18). Therefore, because * This work was supported by Grants-in-Aid for Scientific Research 14209019 (to Y. W). and 13740384 (to T. U.) and by the 21st Century COE program "Establishment of COE on Materials Science: Elucidation and Creation of Molecular Functions" of Nagoya University (to T. D. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. ** Present address: National Institute of Advanced Industrial Science and Technology Research Institute of Genome-based Biofactory, 2-17 Tsukisamu-Higashi, Toyohira, Sapporo 062-8517, Japan.ʈʈ To whom correspondence should be addressed. Tel.: 81-52-789-3049; Fax: 81-52-789-2953; E-mail: yoshi@nucc.cc.nagoya-u.ac.jp. 1 The abbreviations used are: Mb, myoglobin; Mb WDI, Mb F43W/ H64D/V68I mutant; Mb WL, Mb ...

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Reversible formation of high-valent-iron-oxo porphyrin intermediates in heme-based catalysis: revisiting the kinetic model for horseradish peroxidase

Cited by 27 publications

References 38 publications

Mechanism of and exquisite selectivity for O–O bond formation by the heme-dependent chlorite dismutase

Mechanism of and exquisite selectivity for O–O bond formation by the heme-dependent chlorite dismutase

Heme‐(hydro)peroxide mediated O‐ and N‐dealkylation

Monooxygenation of an Aromatic Ring by F43W/H64D/V68I Myoglobin Mutant and Hydrogen Peroxide

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