Theoretical Evidence that Cu<sup>I</sup>Complexation Promotes Degradation of<i>S</i>-Nitrosothiols

Toubin, Céline; Yeung, David Y.-H.; English, and Ann M.; Peslherbe, Gilles H.

doi:10.1021/ja027386t

Cited by 40 publications

(42 citation statements)

References 32 publications

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“… 49 Selected RSNO-Cu(I) complexes have been investigated theoretically, and it was found that coordination of the S atom to Cu(I) lengthens the S-N bond and concomitantly strengthens the N-O bond, thus promoting decomposition. 50 On the other hand, Cu(I) binding to N in the -SNO group is found to dramatically shorten and thus strengthen the S-N bond with a concomitant lengthening of the N-O bond, suggesting the stabilization of the RSNOs versus NO release. 51 However, the barrier for interconversion of Cu(I) binding from N to S is relatively small, which makes the control of the binding modes between nitrosothiols and copper complexes difficult, and consequently Cu(I)-bound RSNO species are inherently unstable.…”

Section: Discussionmentioning

confidence: 97%

Reversible S-nitrosylation in an engineered azurin

et al. 2016

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S-nitrosothiols are known as reagents for NO storage and transportation, and as regulators in many physiological processes. While the S-nitrosylation catalyzed by heme proteins is well known, no direct evidence of S-nitrosylation in copper proteins has been reported. Here we report reversible insertion of NO into a copper-thiolate bond in an engineered copper center in Pseudomonas aeruginosa azurin by rational design of the primary coordination sphere and tuning its reduction potential via deleting a hydrogen bond in the secondary coordination sphere. The results not only provide the first direct evidence of S-nitrosylation of Cu(II)-bound cysteine within metalloproteins, but also shed light on the reaction mechanism and structural features responsible for stabilizing the elusive Cu(I)-S(Cys)NO species. The fast, efficient, and reversible S-nitrosylation reaction is used to demonstrate its ability to prevent NO inhibition of cytochrome bo3 oxidase activity by competing for NO binding with the native enzyme under physiologically relevant conditions.

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Section: Discussionmentioning

confidence: 97%

Reversible S-nitrosylation in an engineered azurin

et al. 2016

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“…Studies of RSNO interacting with metals especially highlighted the dramatic influence of surroundings on the S-N bond nature. For instance, coordination to Cu I , which is known to play important roles in NO-release regulation by catalyzing the decomposition of RSNOs, tends to weaken the S-N bond upon S-coordination while N-coordination was predicted to strengthen it ( 182 , 200 ).…”

Section: Computational Structural and Chemical Studies Of Smentioning

confidence: 99%

Computational Structural Biology of S-nitrosylation of Cancer Targets

et al. 2018

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Nitric oxide (NO) plays an essential role in redox signaling in normal and pathological cellular conditions. In particular, it is well known to react in vivo with cysteines by the so-called S-nitrosylation reaction. S-nitrosylation is a selective and reversible post-translational modification that exerts a myriad of different effects, such as the modulation of protein conformation, activity, stability, and biological interaction networks. We have appreciated, over the last years, the role of S-nitrosylation in normal and disease conditions. In this context, structural and computational studies can help to dissect the complex and multifaceted role of this redox post-translational modification. In this review article, we summarized the current state-of-the-art on the mechanism of S-nitrosylation, along with the structural and computational studies that have helped to unveil its effects and biological roles. We also discussed the need to move new steps forward especially in the direction of employing computational structural biology to address the molecular and atomistic details of S-nitrosylation. Indeed, this redox modification has been so far an underappreciated redox post-translational modification by the computational biochemistry community. In our review, we primarily focus on S-nitrosylated proteins that are attractive cancer targets due to the emerging relevance of this redox modification in a cancer setting.

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“…The solvation energies in water were calculated with the B3LYP (CPCM) /6-31+G* method with Pauling (Merz-Kollman) atomic radii to mimic a polar environment. 13 The global minima of these species (1-5) are given in Fig. 2.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Thionitroxides, RSNHO^•: The Structure of the SNO Moiety in “S-Nitrosohemoglobin”, A Possible NO Reservoir and Transporter

Zhao

Houk

2006

J. Am. Chem. Soc.

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Considerable evidence suggests that the S-nitrosation of cysteine residues, thought to regulate the activities of many proteins, is involved in the uptake and intracellular trafficking of NO. 1 Indeed, to absorb the neutral NO with thiols, a redox reaction is needed to form Snitrosothiols (RSNOs). [1][2][3] A structure of S-nitrosocysteine in hemoglobin proteins was first reported by Arnone and coworkers in 1998. 4a Interestingly, the resulting protein structure obtained under nonbiological conditions (NO pressure, anaerobic) exhibits unexpected C-S-N-O dihedral angles of 88° and -76° for Cys93 of β1 and β2 subunits. The crystallographic results contradict the planar geometries of all RSNOs in small molecule crystallographic data, 5 and from quantum mechanical calculations. 6 Recently, Arnone et al. refined the X-ray data again and reported that the electron density of the SNO-Cys98(F9)β could not be fit with a planar syn or an anti S-nitrosothiol model. They found C-S-N-O dihedral angles between 70° and 90° for SNO-Cys93(F9)β1 and SNO-Cys93(F9)β2. (Fig. 1) 4b To explain this, they proposed that a N-centered radical, Cys-S-N·-OH, was present and stabilized by hydrogen bonding with Val98. Such a radical was previously proposed as an intermediate in reactions of NO with thiols. 7 However, the SNO moiety in the Cys93(F9)β2 subunit is unlikely to be stabilized in this way, because the shortest O---O distance between the oxygen atom of the studied SNO species and the nearest oxygen of Lys144 is about 3.84 Å, a distance too long for significant OH---O hydrogen bonding interactions.By contrast, Montfort and coworkers have reported that the nitric oxide transport protein, nitrophorin cNP, 8 couples reduction and oxidation of a heme moiety with reversible Snitrosation of a cysteine residue (PDB: 1Y21). This S-nitrosothiol species has a C-S-N-O dihedral angle of 0°, coinciding with a planar CSNO geometry in small molecule crystallographic data. The cysteine sulfide coordinating to ferric heme is the key to the Snitrosothiol formation in this protein. Unlike nitrophorins, the NO-bound cysteine in hemoglobin is 10 Å (Fe---S) from the closest heme.To determine the identity of the ~90° CSNO moiety in the purported S-nitrosohemoglobin, we have explored all four types of SNO species (RSNO, RS-N·-OH, RS-NH-O·, and RS-NH-OH) that could be candidates for the observed SNO species, using simple models (R = Me) that can be computed at a high level. By comparison of the calculated structures to the experimental crystallographic data, we have discovered that the thionitroxide radical (Cys-S-NH-O·) is consistent with the observed SNO structures in both β1 and β2 subunits.Correspondence to: K. N. Houk. Supporting Information Available: Complete reference 9, the NO-modified hemoglobin, and the detailed structures and energetics of stationary points on potential energy surfaces of the four SNO species. These materials are available free of charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript J Am Chem Soc...

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Theoretical Evidence that Cu^IComplexation Promotes Degradation ofS-Nitrosothiols

Cited by 40 publications

References 32 publications

Reversible S-nitrosylation in an engineered azurin

Reversible S-nitrosylation in an engineered azurin

Computational Structural Biology of S-nitrosylation of Cancer Targets

Thionitroxides, RSNHO^•: The Structure of the SNO Moiety in “S-Nitrosohemoglobin”, A Possible NO Reservoir and Transporter

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Theoretical Evidence that CuIComplexation Promotes Degradation ofS-Nitrosothiols

Cited by 40 publications

References 32 publications

Reversible S-nitrosylation in an engineered azurin

Reversible S-nitrosylation in an engineered azurin

Computational Structural Biology of S-nitrosylation of Cancer Targets

Thionitroxides, RSNHO•: The Structure of the SNO Moiety in “S-Nitrosohemoglobin”, A Possible NO Reservoir and Transporter

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Theoretical Evidence that Cu^IComplexation Promotes Degradation ofS-Nitrosothiols

Thionitroxides, RSNHO^•: The Structure of the SNO Moiety in “S-Nitrosohemoglobin”, A Possible NO Reservoir and Transporter