Coordination chemistry of the HNO ligand with hemes and synthetic coordination complexes

Farmer, Patrick J.; Sulc, Filip

doi:10.1016/j.jinorgbio.2004.11.005

Cited by 138 publications

(190 citation statements)

References 134 publications

(183 reference statements)

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“…8). Alternatively, the ferrous NO complex could form by reaction of nitroxyl with the ferric enzyme (52). There was a significant difference between the spectral changes seen for HX1 and HX2.…”

Section: Table 4 Affinity and Kinetic Estimates For Hydroxamate Bindimentioning

confidence: 98%

Potent Reversible Inhibition of Myeloperoxidase by Aromatic Hydroxamates

Forbes

Sjögren

Auchère

et al. 2013

Journal of Biological Chemistry

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Background: Myeloperoxidase causes oxidative damage in many inflammatory diseases. Results: New substituted aromatic hydroxamates are identified as potent, selective, and reversible inhibitors of MPO. Conclusion: Binding affinities of hydroxamates to the heme pocket determine the potency of inhibition. Significance: Compounds that bind tightly to the active site of myeloperoxidase have potential as therapeutically useful inhibitors of oxidative stress.

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Section: Table 4 Affinity and Kinetic Estimates For Hydroxamate Bindimentioning

confidence: 98%

Potent Reversible Inhibition of Myeloperoxidase by Aromatic Hydroxamates

Forbes

Sjögren

Auchère

et al. 2013

Journal of Biological Chemistry

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“…Early studies on partially purified protein suggested that HNO was not able to directly activate sGC (31). However, later demonstrations by Farmer and Sulc (43) that HNO could bind to ferrous myoglobin (Mb) led to further analysis of the interaction of HNO with sGC. Fukuto and coworkers (104) have recently demonstrated that two structurally unrelated HNO donors are able to activate purified sGC.…”

Section: The Cardiovascular Systemmentioning

confidence: 99%

The Specificity of Nitroxyl Chemistry Is Unique Among Nitrogen Oxides in Biological Systems

Flores-Santana

Salmon

Donzelli

et al. 2011

Antioxidants & Redox Signaling

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The importance of nitric oxide in mammalian physiology has been known for nearly 30 years. Similar attention for other nitrogen oxides such as nitroxyl (HNO) has been more recent. While there has been speculation as to the biosynthesis of HNO, its pharmacological benefits have been demonstrated in several pathophysiological settings such as cardiovascular disorders, cancer, and alcoholism. The chemical biology of HNO has been identified as related to, but unique from, that of its redox congener nitric oxide. A summary of these findings as well as a discussion of possible endogenous sources of HNO is presented in this review.

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“…The unique reactivity of the Mn-QDO suggests a metalmediated electron transfer mechanism rather than metal-activation of the substrate's inherent base-catalyzed reactivity. There has been much discussion over the electronic nature of bonding in transition metal HNO complexes (50), for instance in the putative catalytic intermediate in nitric oxide reductase P450nor (51). An HNO-Mn II species with a d 5 electronic configuration is unprecedented, as all isolable HNO-metal complexes are diamagnetic with low-spin d 6 metal ions.…”

Section: Discussionmentioning

confidence: 99%

Nitrosyl hydride (HNO) replaces dioxygen in nitroxygenase activity of manganese quercetin dioxygenase

Kumar

Zapata

Ramirez

et al. 2011

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

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Quercetin dioxygenase (QDO) catalyzes the oxidation of the flavonol quercetin with dioxygen, cleaving the central heterocyclic ring and releasing CO. The QDO from Bacillus subtilis is unusual in that it has been shown to be active with several divalent metal cofactors such as Fe, Mn, and Co. Previous comparison of the catalytic activities suggest that Mn(II) is the preferred cofactor for this enzyme. We herein report the unprecedented substitution of nitrosyl hydride (HNO) for dioxygen in the activity of Mn-QDO, resulting in the incorporation of both N and O atoms into the product. Turnover is demonstrated by consumption of quercetin and other related substrates under anaerobic conditions in the presence of HNO-releasing compounds and the enzyme. As with dioxygenase activity, a nonenzymatic base-catalyzed reaction of quercetin with HNO is observed above pH 7, but no enhancement of this basal reactivity is found upon addition of divalent metal salts. Unique and regioselective N-containing products ( 14 N∕ 15 N) have been characterized by MS analysis for both the enzymatic and nonenzymatic reactions. Of the several metallo-QDO enzymes examined for nitroxygenase activity under anaerobic condition, only the Mn(II) is active; the Fe(II) and Co(II) substituted enzymes show little or no activity. This result represents an enzymatic catalysis which we denote nitroxygenase activity; the unique reactivity of the Mn-QDO suggests a metalmediated electron transfer mechanism rather than metal activation of the substrate's inherent base-catalyzed reactivity.nitroxyl | quercetinase D ioxygenases are enzymes that incorporate both atoms of dioxygen into a targeted substrate, e.g., the enzyme catechol 1,2-dioxygenase cleaves the C-C bond between catechol's two hydroxyl groups forming the dicarboxylate cis,cis-muconic acid (1). Although highly divergent, there are two broadly defined classes of nonheme dioxygenases: those that directly bind dioxygen at the metal center or those in which dioxygen binds to the substrate that has been activated by interaction with the metal center (2). Such questions also apply to quercetin dioxygenase (QDO), which catalyzes the oxidation of the flavonol quercetin (1) with dioxygen ( Fig. 1). During turnover, QDO cleaves the central heterocyclic ring of quercetin, releasing CO, and yielding the corresponding depside. The QDO from Bacillus subtilis is unusual in that it has been shown to be active with several divalent metal cofactors such as Cu, Fe, Mn, and Co. Comparison of the catalytic activities suggest that Mn(II) is the preferred cofactor for this enzyme (3).The simple molecule nitrosyl hydride (HNO) is the singly reduced and protonated form of nitric oxide, NO. HNO has garnered much interest because it demonstrates a physiological reactivity distinctly different from its congener nitric oxide (4, 5). In a series of papers, we have reported the preparation and characterization of the HNO adduct of myoglobin (HNO-Mb) by reduction of 7) and by trapping of free HNO by deoxymyoglobin (Mb-Fe II ) (8)...

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Coordination chemistry of the HNO ligand with hemes and synthetic coordination complexes

Cited by 138 publications

References 134 publications

Potent Reversible Inhibition of Myeloperoxidase by Aromatic Hydroxamates

Potent Reversible Inhibition of Myeloperoxidase by Aromatic Hydroxamates

The Specificity of Nitroxyl Chemistry Is Unique Among Nitrogen Oxides in Biological Systems

Nitrosyl hydride (HNO) replaces dioxygen in nitroxygenase activity of manganese quercetin dioxygenase

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