Structural basis of activation of mammalian heme peroxidases

Singh, Prashant K.; Iqbal, Naseer; Sirohi, H.V.; Bairagya, Hridoy R.; Kaur, Punit; Sharma, Sujata

doi:10.1016/j.pbiomolbio.2017.11.003

Cited by 19 publications

(9 citation statements)

References 32 publications

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“…Their active center is composed so that the protein moiety is not substantially damaged by local fire in the form of Compounds ( Figure 1 ) and its oxidizing ability is directed toward the oxidation of substrates: The heme of the peroxidases is attached to protein moiety by at least two covalent bonds. The covalent linkages stabilize the position of the heme moiety, which is important for improving the redox ability of the heme and for the proper structural architecture of the substrate binding site [ 48 ]. True peroxidases do not have oxidizable amino acids in close proximity to heme that are able to compete with external substrates for Compound I (except for cyclooxygenase).…”

Section: Diversity Of Human Hemoproteins With Peroxidase Activitymentioning

confidence: 99%

“…The heme of the peroxidases is attached to protein moiety by at least two covalent bonds. The covalent linkages stabilize the position of the heme moiety, which is important for improving the redox ability of the heme and for the proper structural architecture of the substrate binding site [ 48 ].…”

Section: Diversity Of Human Hemoproteins With Peroxidase Activitymentioning

confidence: 99%

“…Each subunit is a complex of a light chain and a heavy chain; the latter contains heme. In addition to the two ester linkages that are also present in EPO and LPO, the heme in MPO has a unique sulfonium ion linkage that significantly distorts the prosthetic group from a planar conformation [ 48 , 94 , 95 ]. As a result, myeloperoxidase Compound I is the strongest one- and two-electron oxidant among all peroxidase compounds.…”

Section: Myeloperoxidasementioning

confidence: 99%

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Peroxidase Activity of Human Hemoproteins: Keeping the Fire under Control

Vlasova

2018

Molecules

110

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The heme in the active center of peroxidases reacts with hydrogen peroxide to form highly reactive intermediates, which then oxidize simple substances called peroxidase substrates. Human peroxidases can be divided into two groups: (1) True peroxidases are enzymes whose main function is to generate free radicals in the peroxidase cycle and (pseudo)hypohalous acids in the halogenation cycle. The major true peroxidases are myeloperoxidase, eosinophil peroxidase and lactoperoxidase. (2) Pseudo-peroxidases perform various important functions in the body, but under the influence of external conditions they can display peroxidase-like activity. As oxidative intermediates, these peroxidases produce not only active heme compounds, but also protein-based tyrosyl radicals. Hemoglobin, myoglobin, cytochrome c/cardiolipin complexes and cytoglobin are considered as pseudo-peroxidases. Рeroxidases play an important role in innate immunity and in a number of physiologically important processes like apoptosis and cell signaling. Unfavorable excessive peroxidase activity is implicated in oxidative damage of cells and tissues, thereby initiating the variety of human diseases. Hence, regulation of peroxidase activity is of considerable importance. Since peroxidases differ in structure, properties and location, the mechanisms controlling peroxidase activity and the biological effects of peroxidase products are specific for each hemoprotein. This review summarizes the knowledge about the properties, activities, regulations and biological effects of true and pseudo-peroxidases in order to better understand the mechanisms underlying beneficial and adverse effects of this class of enzymes.

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Section: Diversity Of Human Hemoproteins With Peroxidase Activitymentioning

confidence: 99%

Section: Diversity Of Human Hemoproteins With Peroxidase Activitymentioning

confidence: 99%

Section: Myeloperoxidasementioning

confidence: 99%

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Peroxidase Activity of Human Hemoproteins: Keeping the Fire under Control

Vlasova

2018

Molecules

110

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“…However, the time course of the reactions at high H 2 O 2 concentrations (over 2 mM) shows an early plateau of activity, an indication of inactivation of the DNAzymes at high oxidant concentration. Suicide inactivation of natural protein peroxidases and G-quadruplex peroxidase DNAzymes at high H 2 O 2 concentration is a well-known phenomenon that limits the use of peroxidases in certain applications [1,6,8]. In addition, high concentration of H 2 O 2 is known to accelerate the disproportionation of ABTS • radical cation [23].…”

Section: Effects Of Reactants' Concentrations On Activities Of As1411mentioning

confidence: 99%

“…Haem peroxidases use protein scaffolds that activate haem to react with H 2 O 2 [1]. The reaction mechanism and properties of peroxidases have been extensively studied and they have several practical uses in research, bioanalysis and industrial applications.…”

Section: Introductionmentioning

confidence: 99%

Catalytic Activities of Multimeric G-Quadruplex DNAzymes

et al. 2019

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G-quadruplex DNAzymes are short DNA aptamers with repeating G4 quartets bound in a non-covalent complex with hemin. These G4/Hemin structures exhibit versatile peroxidase-like catalytic activity with a wide range of potential applications in biosensing and biotechnology. Current efforts are aimed at gaining a better understanding of the molecular mechanism of DNAzyme catalysis as well as devising strategies for improving their catalytic efficiency. Multimerisation of discrete units of G-quadruplexes to form multivalent DNAzyes is an emerging design strategy aimed at enhancing the peroxidase activities of DNAzymes. While this approach holds promise of generating more active multivalent G-quadruplex DNAzymes, few examples have been studied and it is not clear what factors determine the enhancement of catalytic activities of multimeric DNAzymes. In this study, we report the design and characterisation of multimers of five G-quadruplex sequences (AS1411, Bcl-2, c-MYC, PS5.M and PS2.M). Our results show that multimerisation of G-quadruplexes that form parallel structure (AS1411, Bcl-2, c-MYC) leads to significant rate enhancements characteristic of cooperative and/or synergistic interactions between the monomeric units. In contrast, multimerisation of DNA sequences that form non-parallel structures (PS5.M and PS2.M) did not exhibit similar levels of synergistic increase in activities. These results show that design of multivalent G4/Hemin structures could lead to a new set of versatile and efficient DNAzymes with enhanced capacity to catalyse peroxidase-mimic reactions.

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Cross‐talk Between (Hydrogen)Sulfite and Metalloproteins: Impact on Human Health

Maiti

2022

Chemistry A European J

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Sulfite is a potent toxic substance causing harm to multi-organ in human. Despite toxicity, it is widely used as preservative, anti-browning and anti-oxidant in foods, beverages, and pharmaceuticals, which cause easy admission of sulfite in human. Sulfite is also produced endogenously during the catabolism of cysteine and methionine. In vivo, the serum sulfite level at physiological range is strictly maintained by a molybdenum dependent sulfite oxidase (SO), which catalyzes sulfite to sulfate oxidation via a two-electron oxidation pathway. The loss of SO activity causes high serum sulfite level that fosters several diseases, including asthma, neurological dysfunction, birth defects, and heart diseases. The cytotoxicity of (bi)sulfite is implicated as sulfite radicals, which are generated by mainly heme-peroxidases via a oneelectron oxidation pathway. On the other hand, the toxic sulfite radicals are neutralized to sulfite by heme-globins. The enzymatic reduction of sulfite to sulfide is catalyzed by sulfite reductase, which contains an unusual metal cofactor, siroheme-[4Fe4S]-cluster. Overall, the interaction of sulfite with various metalloproteins in vivo is a close relation with human health. Therefore, this review describes the metabolic conversion of (bi)sulfite to sulfate, sulfite radical or sulfide via oxidation or reduction pathways by various metalloproteins (specially SOs, peroxidases, heme-globins, and sulfite reductases), and the potential applications of sulfite in biosensors/ biofuel cells, anti-browning, and advance oxidation process.

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Structural basis of activation of mammalian heme peroxidases

Cited by 19 publications

References 32 publications

Peroxidase Activity of Human Hemoproteins: Keeping the Fire under Control

Peroxidase Activity of Human Hemoproteins: Keeping the Fire under Control

Catalytic Activities of Multimeric G-Quadruplex DNAzymes

Cross‐talk Between (Hydrogen)Sulfite and Metalloproteins: Impact on Human Health

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