Formation of Nitric Oxide from Nitrite by the Ferriheme <i>b</i> Protein Nitrophorin 7

He, Chunmao; Knipp, Markus

doi:10.1021/ja9040362

Cited by 34 publications

(27 citation statements)

References 30 publications

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“…Afterward, the reaction continues until all the heme centers are NO coordinated (see Fig. 2C, III) (43). This experiment shows that NPs act as catalysts for the nitrite disproportionation reaction at neutral pH.…”

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confidence: 64%

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Nitrophorins: Nitrite disproportionation reaction and other novel functionalities of insect heme‐based nitric oxide transport proteins

Knipp

2011

IUBMB Life

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SummaryNitrophorins (NPs) comprise a unique class of heme proteins used by the blood-sucking insect Rhodnius prolixus to deliver the signaling gas molecule NO into the blood vessel of a host during feeding. Upon NO release, histamine can be scavenged by coordination to the heme iron. Although the protein is of similar size as the mammalian globin monomers and shares the same cofactor and proximal histidine coordination, nitrophorin structure, in contrast, is almost entirely composed of a b-barrel. Comparison of the NO and histamine association constants with the concentrations of both compounds in vivo raises concerns about the very simple ligand release model in case of at least some of the NPs. Therefore, novel functionalities of the NPs were sought. As a result, catalysis of the nitrite disproportionation reaction was found, which leads to the formation of NO with nitrite as the sole substrate. This is the first example of a ferriheme protein that can perform this reaction. Furthermore, although NPs stabilize the ferriheme state, a peroxidase reactivity of the cofactor involving the higher oxidation state iron (Compound I/II) was studied with the potential to catalyze the oxidation of histamine and norepinephrine. In contrast to many other heme proteins including the globins, the ferroheme state was found to be extremely sensitive to O 2 , which is a consequence of the much lower reduction potential of the NPs, so that the 1-electron reduction of O 2 to O À 2 becomes a thermodynamically favored process. Altogether, the detailed study of the NPs gives insight into the structure-function relationships required for the targeted delivery of diatomic gas molecules in biology. Moreover, the comparison of the structure-function relationships of the NPs (NO transporters) with those of the globins (O 2 transporters) will help to elucidate the architectural requirement for the respective tasks.

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confidence: 64%

“…At this time point, similar to the reaction displayed in (B), the rate of the Soret band development increases until NP7 is saturated with NO . [For further experimental details see (43).] 2.…”

Section: Interactions Of Nps With High-molecular Weight Blood Componentsmentioning

confidence: 99%

Nitrophorins: Nitrite disproportionation reaction and other novel functionalities of insect heme‐based nitric oxide transport proteins

Knipp

2011

IUBMB Life

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“…The mechanisms shown here are based on those that are heme-based, molybdopterin-based, and those that function as nitrite anhydrases including nitrophorin [131, 132]. …”

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confidence: 99%

Mechanisms of nitrite bioactivation

2014

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It is now accepted that the anion nitrite, once considered an inert oxidation product of nitric oxide (NO), contributes to hypoxic vasodilation, physiological blood pressure control, and redox signaling. As such, its application in therapeutics is being actively testing in pre-clinical models and in human phase I–II clinical trials. Major pathways for nitrite bioactivation involve its reduction to NO by members of the hemoglobin or molybdopterin family of proteins, or catalyzed dysproportionation. These conversions occur preferentially under hypoxic and acidic conditions. A number of enzymatic systems reduce nitrite to NO and their activity and importance are defined by oxygen tension, specific organ system and allosteric and redox effectors. In this work, we review different proposed mechanisms of nitrite bioactivation, focusing on analysis of kinetics and experimental evidence for the relevance of each mechanism under different conditions.

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“…The viability of this reaction has recently been supported by studies of glass embedded MetHb [26]. Interestingly, it has recently been observed that nitrophorin 7, a salivary ferric hemoprotein from a blood-feeding insect, can catalzye the convertion of nitrite to NO, suggesting similar interesting biological signaling properties of a ferric hemoprotein and nitrite [27]. …”

Section: Introductionmentioning

confidence: 99%

An electron paramagnetic resonance study of the affinity of nitrite for methemoglobin

et al. 2010

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Recent data suggests that reactions of nitrite with ferric hemoglobin are potentially important in heme-protein dependent NO signaling. Our group and others are evaluating the role of reductive nitrosylation reactions in the generation of N2O3 as a signaling molecule. The latter reaction is hypothesized to involve reactions on NO, nitrite and methemoglobin to form N2O3 in a anydrase reaction. Of potential importance to these reactions is the affinity of methemoglobin for nitrite and the reactivity of nitrite bound methemoglobin with nitric oxide. In this paper we review work related to the electronic structure of nitrite bound methemoglobin and its dissociation constant. We present new data using electron paramagnetic resonance spectroscopy which confirm that methemoglobin has a much higher affinity for nitrite, under certain conditions, than reported in classical observations. Interestingly the affinity is greatest at lower pH and low nitrite:methemoglobin ratios. These data suggest additional interesting chemistry in the reaction of nitrite with ferric and ferrous heme species. Moreover, this reaction could serve as a paradigm for ferric heme reactions with nitrite.

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Formation of Nitric Oxide from Nitrite by the Ferriheme b Protein Nitrophorin 7

Cited by 34 publications

References 30 publications

Nitrophorins: Nitrite disproportionation reaction and other novel functionalities of insect heme‐based nitric oxide transport proteins

Nitrophorins: Nitrite disproportionation reaction and other novel functionalities of insect heme‐based nitric oxide transport proteins

Mechanisms of nitrite bioactivation

An electron paramagnetic resonance study of the affinity of nitrite for methemoglobin

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