The molecular mechanism of mammalian NO-synthases: A story of electrons and protons

Santolini, Jérôme

doi:10.1016/j.jinorgbio.2010.10.011

Cited by 71 publications

(64 citation statements)

References 245 publications

(418 reference statements)

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“…The NOSoxy domain binds a heme prosthetic group and the redox factor tetrahydrobiopterin (H 4 B) (4,5). The NOSred domain displays similarities with NADPH-cytochrome P450 reductase and transfers NADPH-derived electrons to the heme through flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) during catalysis (5)(6)(7)(8). In addition, human NOS1 has an N-terminal PDZ domain that mediates protein-protein interactions (9).…”

Section: Introductionmentioning

confidence: 99%

Occurrence, structure, and evolution of nitric oxide synthase–like proteins in the plant kingdom

et al. 2016

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Nitric oxide (NO) signaling regulates various physiological processes in both animals and plants. In animals, NO synthesis is mainly catalyzed by NO synthase (NOS) enzymes. Although NOS-like activities that are sensitive to mammalian NOS inhibitors have been detected in plant extracts, few bona fide plant NOS enzymes have been identified. We searched the data set produced by the 1000 Plants (1KP) international consortium for the presence of transcripts encoding NOS-like proteins in over 1000 species of land plants and algae. We also searched for genes encoding NOS-like enzymes in 24 publicly available algal genomes. We identified no typical NOS sequences in 1087 sequenced transcriptomes of land plants. In contrast, we identified NOS-like sequences in 15 of the 265 algal species analyzed. Even if the presence of NOS enzymes assembled from multipolypeptides in plants cannot be conclusively discarded, the emerging data suggest that, instead of generating NO with evolutionarily conserved NOS enzymes, land plants have evolved finely regulated nitrate assimilation and reduction processes to synthesize NO through a mechanism different than that in animals.

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Section: Introductionmentioning

confidence: 99%

Occurrence, structure, and evolution of nitric oxide synthase–like proteins in the plant kingdom

et al. 2016

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“…Their mechanistic aspects are not completely understood, 2 and it is of current interest to study structures of the heme species that activates O 2 and transforms the substrate. 3 Knowledge of the relative structural arrangement of the heme, substrate, and possible other molecules relevant to catalysis is important for understanding the chemical mechanism. One specific, important problem is the role of hydrogen bonding, and in this context, of the active site water molecule, in the catalysis.…”

Section: Introductionmentioning

confidence: 99%

Probing the Hydrogen Bonding of the Ferrous–NO Heme Center of nNOS by Pulsed Electron Paramagnetic Resonance

et al. 2015

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Oxidation of L-arginine (L-Arg) to nitric oxide (NO) by NO synthase (NOS) takes place at the heme active site. It is of current interest to study structures of the heme species that activates O2 and transforms the substrate. The NOS ferrous–NO complex is a close mimic of the obligatory ferric (hydro)peroxo intermediate in NOS catalysis. In this work, pulsed electron–nuclear double resonance (ENDOR) spectroscopy was used to probe the hydrogen bonding of the NO ligand in the ferrous–NO heme center of neuronal NOS (nNOS) without a substrate and with L-Arg or N-hydroxy-L-arginine (NOHA) substrates. Unexpectedly, no H-bonding interaction connecting the NO ligand to the active site water molecule or the Arg substrate was detected, in contrast to the results obtained by X-ray crystallography for the Arg-bound nNOS heme domain [Li et al. J. Biol. Inorg. Chem. 2006, 11, 753–768]. The nearby exchangeable proton in both the no-substrate and Arg-containing nNOS samples is located outside the H-bonding range and, on the basis of the obtained structural constraints, can belong to the active site water (or OH). On the contrary, in the NOHA-bound sample, the nearby exchangeable hydrogen forms an H-bond with the NO ligand (on the basis of its distance from the NO ligand and a nonzero isotropic hfi constant), but it does not belong to the active site water molecule because the water oxygen atom (detected by 17O ENDOR) is too far. This hydrogen should therefore come from the NOHA substrate, which is in agreement with the X-ray crystallography work [Li et al. Biochemistry 2009, 48, 10246–10254]. The nearby nonexchangeable hydrogen atom assigned as Hɛ of Phe584 was detected in all three samples. This hydrogen atom may have a stabilizing effect on the NO ligand and probably determines its position.

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“…NOHA is a well-studied biosynthetic intermediate in the NOS-mediated production of NO (and L-citrulline) from L-arginine (Scheme 1) [23,24]. NOHA, which can be uncoupled from NOS at levels up to 15 μM both in vitro and in vivo [25,26], has also been shown to be a potent inhibitor of arginase, regulating the production of L-arginine [27,28].…”

Section: Introductionmentioning

confidence: 99%

Oxidation of N-hydroxy-l-arginine by hypochlorous acid to form nitroxyl (HNO)

Cline

Chavez

Toscano

2013

Journal of Inorganic Biochemistry

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The molecular mechanism of mammalian NO-synthases: A story of electrons and protons

Cited by 71 publications

References 245 publications

Occurrence, structure, and evolution of nitric oxide synthase–like proteins in the plant kingdom

Occurrence, structure, and evolution of nitric oxide synthase–like proteins in the plant kingdom

Probing the Hydrogen Bonding of the Ferrous–NO Heme Center of nNOS by Pulsed Electron Paramagnetic Resonance

Oxidation of N-hydroxy-l-arginine by hypochlorous acid to form nitroxyl (HNO)

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