The Synthetic and Structural Chemistry of Heme Derivatives with Nitric Oxide Ligands

and, W. Robert Scheidt; Ellison, Mary K.

doi:10.1021/ar9700116

Cited by 176 publications

(192 citation statements)

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“…Typically, the preferred orientation of ferric heme-NO is linear (i.e. Fe(II)-NO ϩ ), whereas the geometry of Fe(II)-NO is bent (38,39). So if, for instance, adoption of a linear geometry is sterically hindered, it may be energetically favorable for the c heme to reduce the d 1 heme-NO complex to form Fe(II)-NO.…”

Section: Discussionmentioning

confidence: 99%

Time-resolved Infrared Spectroscopy Reveals a Stable Ferric Heme-NO Intermediate in the Reaction of Paracoccus pantotrophus Cytochrome cd 1 Nitrite Reductase with Nitrite

George¹,

Allen²,

Ferguson³

et al. 2000

Journal of Biological Chemistry

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Cytochrome cd 1 is a respiratory enzyme that catalyzes the physiological one-electron reduction of nitrite to nitric oxide. The enzyme is a dimer, each monomer containing one c-type cytochrome center and one active site No kinetically competent release of NO could be detected, indicating that at least one additional factor is required for product release by the enzyme. Implications for the mechanism of P. pantotrophus cytochrome cd 1 are discussed.

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Section: Discussionmentioning

confidence: 99%

Time-resolved Infrared Spectroscopy Reveals a Stable Ferric Heme-NO Intermediate in the Reaction of Paracoccus pantotrophus Cytochrome cd 1 Nitrite Reductase with Nitrite

George¹,

Allen²,

Ferguson³

et al. 2000

Journal of Biological Chemistry

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“…Sulfur of Cys-60 is 3.1 Å away from the heme iron in this model and possibly no longer attached. The FeONOO conjugate displays a highly bent geometry (119°) that is consistent with a ferrous-nitrosyl complex (33), and a FeON bond length (1.86 Å) that is slightly long for a five-coordinate heme-NO, suggesting that Cys-60 may still be weakly coordinated to the iron. The Cys-SNO conjugate refines with SON bond length (1.7 Å), SONOO bond angle (114°) and COSONOO dihedral angle (0°, syn geometry) that are typical of model compounds (34,35).…”

Section: Methodsmentioning

confidence: 80%

Heme-assisted S-nitrosation of a proximal thiolate in a nitric oxide transport protein

Weichsel

Maes

Andersen

et al. 2005

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

153

154

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Certain bloodsucking insects deliver nitric oxide (NO) while feeding, to induce vasodilation and inhibit blood coagulation. We have expressed, characterized, and determined the crystal structure of the Cimex lectularius (bedbug) nitrophorin, the protein responsible for NO storage and delivery, to understand how the insect successfully handles this reactive molecule. Surprisingly, NO binds not only to the ferric nitrophorin heme, but it can also be stored as an S-nitroso (SNO) conjugate of the proximal heme cysteine (Cys-60) when present at higher concentrations. EPR-and UV-visible spectroscopies, and a crystallographic structure determination to 1.75-Å resolution, reveal SNO formation to proceed with reduction of the heme iron, yielding an Fe-NO complex. Stopped-flow kinetic measurements indicate that an ordered reaction mechanism takes place: initial NO binding occurs at the ferric heme and is followed by heme reduction, Cys-60 release from the heme iron, and SNO formation. Release of NO occurs through a reversal of these steps. These data provide, to our knowledge, the first view of reversible metal-assisted SNO formation in a protein and suggest a mechanism for its role in NO release from ferrous heme. This mechanism and Cimex nitrophorin structure are completely unlike those of the nitrophorins from Rhodnius prolixus, where NO protection is provided by a large conformational change that buries the heme nitrosyl complex, highlighting the remarkable evolution of proteins that assist insects in bloodfeeding.crystal structure ͉ heme protein ͉ nitrophorin ͉ S-nitrosocysteine ͉ S-nitroso N itric oxide (NO) is a reactive molecule produced at low concentrations in all higher animals for regulating activities such as blood pressure, wound healing, and memory formation, and at higher concentrations to kill infectious invaders (1). Many NO interactions of biological importance involve hemecontaining proteins. NO is synthesized by NO synthase (NOS), a dimeric heme protein that converts L-arginine and oxygen to citrulline and NO (2). NO signaling often involves soluble guanylate cyclase, a heterodimeric heme protein that catalyzes cGMP formation after NO binding at the heme center (3). NO delivery by bloodfeeding insects is through heme-containing nitrophorins (4, 5).Because NO is a free-radical molecule with a half-life of Ͻ1 sec when exposed to biological tissue, protection of the molecule during storage and transport is required. Reaction products of unprotected NO include higher nitrogen oxides, tyrosine nitrations, heme oxidation or reduction, and various S-nitrosations (S-nitroso, SNO). Formation of Cys-SNO from NO and free thiol in vivo has been demonstrated for many proteins (6); however, the functional significance of this attractive model for regulation remains uncertain (7). For example, formation of hemoglobin Cys␤93-SNO (Hb-SNO) has been postulated to be reversible and to be involved in blood pressure regulation; however, tight binding or reaction with oxygen at the hemoglobin ferrous center would seem to pr...

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“…Six-coordinate S ϭ 1͞2 {FeNO} 7 species in heme proteins have much stronger Fe-NO bonds, as evidenced by (Fe-NO) frequencies in the range 536-558 cm Ϫ1 (20,21,41), and much weaker N-O bonds, as evidenced by (N-O) frequencies in the range 1,555-1,624 cm Ϫ1 (20,21). Although no clear consensus has emerged concerning the most appropriate description of the electronic structure and bonding in S ϭ 1͞2 {FeNO} 7 species (18,32,42), the increase in Fe-NO bond strength and concomitant decrease in the N-O bond strength, compared with S ϭ 3͞2 {FeNO} 7 species, appear to be a direct consequence of increased -donation into the empty d z2 orbital that results from lowering the Fe spin state from high to low or intermediate spin.…”

Section: Discussionmentioning

confidence: 99%

“…However, these intermediates are short lived and difficult to study experimentally. Nitric oxide (NO) has been extensively used as a substrate analog of molecular oxygen to form stable nitrosyl derivatives that provide insight into oxygen transport and activation intermediates in many heme (18)(19)(20)(21) and nonheme (22)(23)(24)(25)(26)(27)(28)(29) iron enzymes. Hence, we report here the formation and spectroscopic characterization of a stable NO-bound derivative of the reduced 1Fe-SOR from P. furiosus using the combination of EPR, UV-visible absorption, and variable-temperature, variable-field magnetic CD (VTVH MCD), resonance Raman, and Fourier transform IR (FTIR) spectroscopies.…”

mentioning

confidence: 99%

Nitric oxide binding at the mononuclear active site of reduced Pyrococcus furiosus superoxide reductase

Clay

Cosper

Jenney

et al. 2003

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

133

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O ver the past 4 yr, evidence has accumulated for a novel pathway for detoxification of reactive oxygen species that is specific for anaerobic and microaerophilic microorganisms (1-3). The key enzyme in this pathway is superoxide reductase (SOR), which catalyzes the reduction of superoxide to hydrogen peroxide (4), with rubredoxin as the probable physiological electron donor (2, 5). Although all SORs have a ␤-barrel domain containing a unique type of mononuclear Fe center that serves as the site for superoxide reduction (6, 7), some have an additional N-terminal domain that contains an intrinsic rubredoxin-like mononuclear Fe site, which is ligated by four cysteines in a distorted tetrahedral arrangement analogous to that found in desulforedoxin (6). These two classes are conveniently referred to as 1Fe-and 2Fe-SORs, but they are also known by their trivial names, neelaredoxins and desulfoferrodoxins, respectively.Spectroscopic and crystallographic studies of the 1Fe-SOR from Pyrococcus furiosus (7-9) and the 2Fe-SOR from Desulfovibrio desulfuricans (6, 10, 11) have shown that the mononuclear iron active site is ligated by four equatorial histidines (3 N and 1␦N) and one axial cysteinate in a square-pyramidal arrangement. The sixth coordination site appears to be occupied by a monodentate glutamate in the oxidized state but is vacant or occupied by a weakly coordinated water molecule in the reduced state, thereby providing a site for superoxide binding and reduction. These structural studies, combined with recent mutagenesis and pulse radiolysis kinetic results (12-16), have led to the proposal for the catalytic mechanism shown in Fig. 1 Characterization of enzymatic intermediates is required for both detailed understanding of the mechanism of SOR and addressing the key questions of how and why the SOR active site preferentially catalyzes reduction rather than dismutation of superoxide. However, these intermediates are short lived and difficult to study experimentally. Nitric oxide (NO) has been extensively used as a substrate analog of molecular oxygen to form stable nitrosyl derivatives that provide insight into oxygen transport and activation intermediates in many heme (18-21) and nonheme (22-29) iron enzymes. Hence, we report here the formation and spectroscopic characterization of a stable NO-bound derivative of the reduced 1Fe-SOR from P. furiosus using the combination of EPR, UV-visible absorption, and variable-temperature, variable-field magnetic CD (VTVH MCD), resonance Raman, and Fourier transform IR (FTIR) spectroscopies. The structural and electronic characterization of the NO adduct of SOR facilitates understanding of how the active site is tuned for oxidative addition of superoxide and release rather than intraligand cleavage of the peroxide product. Materials and MethodsBiochemical Techniques and Sample Preparation. Recombinant natural abundance and 34 S globally enriched P. furiosus SOR was This paper was submitted directly (Track II) to the PNAS office.Abbreviations: SOR, superoxide reductase; V...

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The Synthetic and Structural Chemistry of Heme Derivatives with Nitric Oxide Ligands

Abstract: The first nitrosyl porphyrin characterized was the {CoNO} 8 derivative, [Co(TPP)(NO)], 15 followed by the {FeNO} 7 complex, [Fe(TPP)(NO)]. 16 An undergraduate, Mark Frisse, developed simple anaerobic techniques necessary for

Cited by 176 publications

References 54 publications

Time-resolved Infrared Spectroscopy Reveals a Stable Ferric Heme-NO Intermediate in the Reaction of Paracoccus pantotrophus Cytochrome cd 1 Nitrite Reductase with Nitrite

Time-resolved Infrared Spectroscopy Reveals a Stable Ferric Heme-NO Intermediate in the Reaction of Paracoccus pantotrophus Cytochrome cd 1 Nitrite Reductase with Nitrite

Heme-assisted S-nitrosation of a proximal thiolate in a nitric oxide transport protein

Nitric oxide binding at the mononuclear active site of reduced Pyrococcus furiosus superoxide reductase

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