Nitric oxide dioxygenase function and mechanism of flavohemoglobin, hemoglobin, myoglobin and their associated reductases

Gardner, Paul R.

doi:10.1016/j.jinorgbio.2004.10.003

Cited by 244 publications

(197 citation statements)

References 228 publications

(413 reference statements)

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“…The same conclusion can be drawn for an oxidative (42) or for the production of NO 2 -Tyr on a plant Hb (46). In these two cases, the nitrating agent is proposed to be the NO 2 • radical based on the peroxidase activity (pathway 3) of the hemoproteins (42,46). In fact, in these and our own studies, the possibility that H 2 O 2 might be generated inside the heme pocket cannot be entirely ruled out.…”

Section: Discussionsupporting

confidence: 70%

“…In nodules, NO 2 − and NO• are mainly produced as a result of the nitrate reductase activities in the cytosol and bacteroids (50)(51)(52). Under natural conditions, nitration reactions are likely to occur because Lb may be exposed to NO 2 − over weeks or months and because the pH decreases to 5.5 during nodule senescence (53). The identification of Lbs bearing a nitrovinyl in their hemes provides conclusive evidence that nitrating and oxidizing RNS are produced in nodules.…”

Section: Discussionmentioning

confidence: 99%

“…Not surprisingly, they are structurally and functionally diverse. Flavohemoglobins of bacteria and yeast are chimeric Hbs with heme and FAD reductase domains, and are involved in nitric oxide (NO•) metabolism because of their high NO• dioxygenase activity (2). In humans and other vertebrates, Hb and Mb play key roles in efficient O 2 transport and storage but are also involved in NO• homeostasis, whereas the recently discovered neuroglobin and cytoglobin might assist in O 2 transport to the mitochondria and act as NADH oxidases and O 2 sensors (2, 3).…”

mentioning

confidence: 99%

“…Nonsymbiotic Hbs are further classified into two groups based on phylogeny and O 2 -binding properties. Class 1 Hbs are expressed at ∼100 nM in most plant tissues, display extremely high affinity for O 2 , and participate in NO• metabolism and in the maintenance of cell energetics under hypoxia (5-7), whereas class 2 Hbs have similar O 2 affinities to Lbs but unknown function (8). Plant truncated Hbs resemble their bacterial counterparts in having a 2/2 helical sandwich secondary structure instead of the canonical 3/3 structure of other Hbs, and have not yet been assigned any role (1).…”

mentioning

confidence: 99%

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Leghemoglobin green derivatives with nitrated hemes evidence production of highly reactive nitrogen species during aging of legume nodules

Navascués

Pérez-Rontomé

Gay

et al. 2012

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

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Globins constitute a superfamily of proteins widespread in all kingdoms of life, where they fulfill multiple functions, such as efficient O 2 transport and modulation of nitric oxide bioactivity. In plants, the most abundant Hbs are the symbiotic leghemoglobins (Lbs) that scavenge O 2 and facilitate its diffusion to the N 2 -fixing bacteroids in nodules. The biosynthesis of Lbs during nodule formation has been studied in detail, whereas little is known about the green derivatives of Lbs generated during nodule senescence. Here we characterize modified forms of Lbs, termed Lba m , Lbc m , and Lbd m , of soybean nodules. These green Lbs have identical globins to the parent red Lbs but their hemes are nitrated. By combining UV-visible, MS, NMR, and resonance Raman spectroscopies with reconstitution experiments of the apoprotein with protoheme or mesoheme, we show that the nitro group is on the 4-vinyl. In vitro nitration of Lba with excess nitrite produced several isomers of nitrated heme, one of which is identical to those found in vivo. The use of antioxidants, metal chelators, and heme ligands reveals that nitration is contingent upon the binding of nitrite to heme Fe, and that the reactive nitrogen species involved derives from nitrous acid and is most probably the nitronium cation. The identification of these green Lbs provides conclusive evidence that highly oxidizing and nitrating species are produced in nodules leading to nitrosative stress. These findings are consistent with a previous report showing that the modified Lbs are more abundant in senescing nodules and have aberrant O 2 binding.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Leghemoglobin green derivatives with nitrated hemes evidence production of highly reactive nitrogen species during aging of legume nodules

Navascués

Pérez-Rontomé

Gay

et al. 2012

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

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“…This primordial oxygenase activity is still apparent in the capacity of hemoglobin [6] and myoglobin [4] to scavenge NO, and appears to have pathophysiological significance, since overexpression of inducible NO synthase (NOS) causes heart failure in myoglobin-knockout mice [7]. Because Ngb binds NO [23], its neuroprotective action may also relate to NO scavenging [1,8].…”

Section: Introductionmentioning

confidence: 99%

Neuroglobin protects against nitric oxide toxicity

Jin

Mao

Xie

et al. 2008

Neuroscience Letters

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Neuroglobin (Ngb) is a novel vertebrate globin expressed principally in neurons. Ngb expression is induced by hypoxia and ischemia, and Ngb protects neurons against these insults. The mechanism of Ngb's protective action is unknown, but its ability to bind NO suggests that NO scavenging might be involved. To test this hypothesis, we treated wild type and Ngb-transfected HN33 (mouse hippocampal neuron × N18TG2 neuroblastoma) cells with NO donors and compared their sensitivity to NO-induced cell death. Ngb overexpression shifted concentration-toxicity curves to the right, indicating reduced susceptibility to NO or is metabolites. The results suggest that the ability of Ngb to neutralize the neurotoxic effects of reactive nitrogen species may be an important contributor to its neuroprotective properties. KeywordsNeuroglobin; nitric oxide; hypoxia Neuroglobin (Ngb) is a monomeric globin that is distantly related to hemoglobin and myoglobin and is expressed predominantly in brain neurons [3]. Ngb expression is induced by neuronal hypoxia and cerebral ischemia [21] and Ngb, in turn, appears to modulate hypoxicischemic brain injury. Thus, enhancing Ngb expression reduces-and knocking down Ngb expression increases-hypoxic neuronal injury in vitro [21] and ischemic cerebral injury in vivo [22]. In addition, Ngb-overexpressing transgenic mice are resistant to cerebral infarction from occlusion of the middle cerebral artery [10,11]. Ngb also reduces the toxicity of H 2 O 2 [5], paraquat [5] and β-amyloid [13] in vitro. However, the mechanisms that underlie neuroprotection by Ngb are unknown.Ancestral globins served primarily as NO oxygenases, converting NO to nitrate, whereas their O 2 -transporting function evolved later [20]. This primordial oxygenase activity is still apparent in the capacity of hemoglobin [6] and myoglobin [4] to scavenge NO, and appears to have pathophysiological significance, since overexpression of inducible NO synthase (NOS) causes heart failure in myoglobin-knockout mice [7]. Because Ngb binds NO [23], its neuroprotective action may also relate to NO scavenging [1,8].Several lines of evidence point to a connection between Ngb and NO. In addition to the ability of Ngb to bind NO [23], some studies have shown parallelism between the distribution of Ngb and of neuronal NOS (nNOS) [15], and NOS expression is increased in several tissues of Ngboverexpressing transgenic mice [11]. Autooxidation of Ngb yields NgbO 2 , which is thought to react rapidly with NO to form a peroxynitrite (ONOO − )-bound intermediate that decays to * To whom correspondence should be addressed: dgreenberg@buckinstitute.org 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 ...

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Interdomain electron transfer in flavohaemoglobin from Candida norvegensis with antibiotic azole compounds

2022

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Flavohaemoglobins (FlavoHbs) function as nitric oxide dioxygenases, oxidizing nitric oxide with nitrite and shuttling electrons from NAD(P)H via FAD and O 2 . Here, using pulse radiolysis, we investigate intramolecular electron transfer between FAD and haem b in FlavoHbs. We found that reduction of FlavoHb with hydrated electrons proceeded via two phases: an initial fast phase and a second slower process. Absorbance measured at 600 nm revealed fast flavin reduction followed by a slower decrease corresponding to reoxidation of FAD. The slower process was partially lost in FlavoHbs lacking FAD. These results suggest that the slower phase is attributable to intramolecular electron transfer from FAD to the haem iron. The rate constant in the absence of azole compound (3.3 × 10 3 s -1 ) was accelerated ~10fold (2.7 × 10 4 s -1 ) by the binding of econazole, reflecting a conformational change in the open-to-closed transition.

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Nitric oxide dioxygenase function and mechanism of flavohemoglobin, hemoglobin, myoglobin and their associated reductases

Cited by 244 publications

References 228 publications

Leghemoglobin green derivatives with nitrated hemes evidence production of highly reactive nitrogen species during aging of legume nodules

Leghemoglobin green derivatives with nitrated hemes evidence production of highly reactive nitrogen species during aging of legume nodules

Neuroglobin protects against nitric oxide toxicity

Interdomain electron transfer in flavohaemoglobin from Candida norvegensis with antibiotic azole compounds

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