Structures of the high-valent metal-ion haem–oxygen intermediates in peroxidases, oxygenases and catalases

Hersleth, H.-P.; Ryde, Ulf; Rydberg, Patrik; Görbitz, Carl Henrik; Andersson, Karin

doi:10.1016/j.jinorgbio.2006.01.018

Cited by 153 publications

(138 citation statements)

References 82 publications

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“…Iron-nitrido complexes, which are isoelectronic to iron-oxo complexes, are also considered as key intermediates in a number of important biological transformations. However, while a number of transient high-valent iron-oxo intermediates in the catalytic cycle of haem and non-haem enzymes have been identified and spectroscopically characterized [1][2][3][5][6][7]9,10,18 , direct evidence for the involvement of iron-nitrido intermediates in biology is lacking. Iron-nitride-mediated mechanistic postulates have nevertheless been motivated on the basis of indirect evidences that are obtained from various biochemical experiments [13][14][15][16] .…”

Section: Iron-nitrido Complexesmentioning

confidence: 99%

The biology and chemistry of high-valent iron–oxo and iron–nitrido complexes

2012

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selective functionalization of unactivated c-H bonds and ammonia production are extremely important industrial processes. a range of metalloenyzmes achieve these challenging tasks in biology by activating dioxygen and dinitrogen using cheap and abundant transition metals, such as iron, copper and manganese. High-valent iron-oxo and -nitrido complexes act as active intermediates in many of these processes. the generation of well-described model compounds can provide vital insights into the mechanism of such enzymatic reactions. advances in the chemistry of model high-valent iron-oxo and -nitrido systems can be related to our understanding of the biological systems.H igh-valent oxoiron(IV) and formally oxoiron(V) species have been spectroscopically identified as active intermediates in the catalytic cycles of a number of enzymatic systems 1-10 . Haem and non-haem proteins use these reactive intermediates to couple the activation of dioxygen to the oxidation of their substrates. In most cases, an oxygen atom is inserted into an unactivated C-H bond of the substrate; for example, in hydroxylation reactions [1][2][3][4][5][6][7][8][9][10] . However, many other reactions, including halogenation, desaturation, cyclization, epoxidation and decarboxylation, are also known to involve oxoiron species 1,3 . Superoxidized iron complexes with (valence) isoelectronic imido and nitrido ligands, as well as 'surface nitrides' , have also been implicated as key intermediates in the nitrogen atom transfer reactions 11 , the biological synthesis of ammonia by the nitrogenase enzyme 12-16 and the industrial Haber-Bosch process 17 .The generation of well-described model compounds can provide vital insights into the mechanism of such enzymatic reactions. Consequently, considerable effort has been made by synthetic chemists to prepare viable models for the putative reaction intermediates in the catalytic cycles of O 2 and N 2 activating enzymes. In this review, we provide an overview of all high-valent oxoiron and nitridoiron species that have been either identified or proposed as reactive intermediates in biology. Subsequently, we summarize some of the recent advances in bioinorganic chemistry that have led to the identification and isolation of iron complexes in unusually high formal oxidation states, containing iron-oxygen or iron-nitrogen multiple bonds. The spectroscopic characterization and the reactivity studies of these model complexes provide vital insights into the mechanism that nature uses to induce the reductive cleavage of dioxygen or dinitrogen in carrying out a number of important biochemical oxidative transformations. Moreover, the comparative review of the electronic structures of the isoelectronic oxoiron and nitridoiron functionalities reveals that the Fe-N bonds are intrinsically more covalent than the Fe-O bonds.

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Section: Iron-nitrido Complexesmentioning

confidence: 99%

The biology and chemistry of high-valent iron–oxo and iron–nitrido complexes

2012

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“…Several crystal structures of these intermediates have been solved (22). As mentioned above, active site amino acids of peroxidases are involved in deprotonation/protonation of the iron-linked peroxide in the first step of the reaction cycle.…”

Section: Myoglobin (Mb)mentioning

confidence: 99%

“…In the present study we try to elucidate the structure of Mb compound II by the use of crystallography in combination with spectroscopy and previous theoretical studies (22,48). In the crystallographic studies the potential radiation damage and radiation-induced reduction of the metal-center must be addressed.…”

Section: Myoglobin (Mb)mentioning

confidence: 99%

“…The importance of these questions and the use of single-crystal microspectrophotometry was acknowledged early in the study of these peroxidase, oxygenase, and catalase intermediates (52)(53)(54). The actual rate by which these intermediates are reduced varies considerably among proteins (22). The use of single-crystal microspectrophotometry is therefore essential to determine the redox-state correctly in each case.…”

Section: Myoglobin (Mb)mentioning

confidence: 99%

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Crystallographic and Spectroscopic Studies of Peroxide-derived Myoglobin Compound II and Occurrence of Protonated FeIV–O

Hersleth

Uchida

Røhr

et al. 2007

Journal of Biological Chemistry

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“…Both TXAS and PGIS utilize an endoperoxide (PGH 2 ) as their substrate, and some aspects of peroxidase-based mechanisms may be relevant. Most peroxidases have heme Fe(III) as the prosthetic group and catalyze a two-electron oxidation to produce an intermediate called Compound I (Cpd I) [5]. Subsequent one-electron reduction of Cpd I generates Compound II (Cpd II), which contains an Fe(IV)-oxo complex.…”

mentioning

confidence: 99%

Reaction mechanisms of 15-hydroperoxyeicosatetraenoic acid catalyzed by human prostacyclin and thromboxane synthases

Yeh¹,

Tsai²,

Wang³

2007

Archives of Biochemistry and Biophysics

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Prostacyclin synthase (PGIS) and thromboxane synthase (TXAS) are atypical cytochrome P450s. They do not require NADPH or dioxygen for isomerization of prostaglandin H 2 (PGH 2 ) to produce prostacyclin (PGI 2 ) and thromboxane A 2 (TXA 2 ). PGI 2 and TXA 2 have opposing actions on platelet aggregation and blood vessel tone. In this report, we use a lipid hydroperoxide, 15-hydroperoxyeicosatetraenoic acid (15-HPETE), to explore the active site characteristics of PGIS and TXAS. The two enzymes transformed 15-HPETE not only into 8,, like many microsomal P450s, but also to 15-ketoeicosatetraenoic acid (15-KETE) and 15-hydroxyeicosatetraenoic acid (15-HETE). 13-OH-14,15-EET and 15-KETE result from homolytic cleavage of the O-O bond, whereas 15-HETE results from heterolytic cleavage, a common peroxidase pathway. About 80% of 15-HPETE was homolytically cleaved by PGIS and 60% was homolytically cleaved by TXAS. The V max of homolytic cleavage is 3.5-fold faster than heterolytic cleavage for PGIS-catalyzed reactions (1100 min −1 vs. 320 min −1 ) and 1.4-fold faster for TXAS (170 min −1 vs. 120 min −1 ). Similar K M values for homolytic and heterolytic cleavages were found for PGIS (∼60 μM 15-HPETE) and TXAS (∼80 μM 15-HPETE), making PGIS a more efficient catalyst for the 15-HPETE reaction.Keywords prostacyclin synthase; thromboxane synthase; cytochrome P450; peroxide bond cleavage; homolytic; heterolytic; hydroperoxides; epoxyalcohol Prostacyclin synthase (PGIS) and thromboxane synthase (TXAS) are members of the cytochrome P450 superfamily, which uses heme as the prosthetic group and has a cysteine thiolate proximal ligand [1,2]. PGIS and TXAS convert prostaglandin H 2 (PGH 2 ) to prostacyclin (PGI 2 ) and thromboxane A 2 (TXA 2 ), respectively. PGI 2 inhibits platelet activation and aggregation and induces vasodilation, whereas TXA 2 stimulates platelet secretion, aggregation and vasoconstriction [3]. Both PGI 2 and TXA 2 are rapidly hydrolyzed To whom correspondence should be addressed: Lee-Ho Wang Division of Hematology Department of Internal Medicine 6431 Fannin Houston, TX 77030 Tel: 713-500-6794 Fax: 713-500-6810 e-mail: lee-ho.wang@uth.tmc.edu 1 The abbreviations used are: PGIS, prostacyclin synthase; PGI 2 , prostacyclin; PGHS, prostaglandin H synthase; TXAS, thromboxane synthase; TXA 2 , thromboxane A 2 ; 8,11-eicosatrienoic acid; ESI/MS, electron-spray ionization/ mass spectrometry; EPR, electron paramagnetic resonance; SVD, singular value decomposition.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Hecker and Ullrich proposed a caged radical mechanism for TXAS ...

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Structures of the high-valent metal-ion haem–oxygen intermediates in peroxidases, oxygenases and catalases

Cited by 153 publications

References 82 publications

The biology and chemistry of high-valent iron–oxo and iron–nitrido complexes

The biology and chemistry of high-valent iron–oxo and iron–nitrido complexes

Crystallographic and Spectroscopic Studies of Peroxide-derived Myoglobin Compound II and Occurrence of Protonated FeIV–O

Reaction mechanisms of 15-hydroperoxyeicosatetraenoic acid catalyzed by human prostacyclin and thromboxane synthases

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