Trp180 of endothelial NOS and Trp56 of bacterial saNOS modulate sigma bonding of the axial cysteine to the heme

Lang, Jérôme; Driscoll, Danelle; Gélinas, Stéphanie; Rafferty, Steven P.; Couture, Manon

doi:10.1016/j.jinorgbio.2009.05.011

Cited by 14 publications

(33 citation statements)

References 64 publications

(107 reference statements)

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“…The affinity of imidazole for bsNOS heme is the greatest for W66H (weak -competition), decreases for WT, and decreases even more for W66F and W66Y (strong -competition). However, we do not observe a better stabilization of Fe II CO and Fe II NO species for W66Y; no H-bond with the tyrosine proton, such as the one observed for eNOS (53), can be deduced from our data. Our work clearly indicates that the tryptophan-thiolate H-bond interaction controls the stability of bsNOS Fe II -XO complexes, such as Fe II NO, Fe II CO, and most probably Fe II O 2 .…”

Section: Role Of Tryptophan-thiolate H-bond In Bsnoscontrasting

confidence: 84%

“…If bacNOSs are bona fide oxygenases, the same regulation pattern should prevail. This has been suggested by Couture and coworkers (53), who showed that the suppression of the Trp-Cys H-bond in saNOS seemed to modify its proximal Fe-S bond.…”

mentioning

confidence: 63%

“…66 of bsNOS is engaged in an H-bond with the heme proximal ligand that is believed to tune the properties of the NOS Fe-S bond (53). We present here for the first time a comparative analysis of five different mutants of this residue that differentially affect the environment of the proximal ligand: (i) the F and Y mutants, already described for nNOS (70) and recently for eNOS and saNOS (53), correspond to a suppression of the H-bond; (ii) the H mutant, described for iNOS (52), is supposed to induce a strengthening of the H-bond; (iii) finally, the A and L mutants, as yet undescribed, should suppress both H-bond and -stacking interactions.…”

Section: Trpmentioning

confidence: 99%

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The Proximal Hydrogen Bond Network Modulates Bacillus subtilis Nitric-oxide Synthase Electronic and Structural Properties

Brunel

Wilson

Henry

et al. 2011

Journal of Biological Chemistry

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Bacterial nitric-oxide synthase (NOS)-like proteins are believed to be genuine NOSs. As for cytochromes P450 (CYPs), NOS-proximal ligand is a thiolate that exerts a push effect crucial for the process of dioxygen activation. Unlike CYPs, this catalytic electron donation seems controlled by a hydrogen bond (H-bond) interaction between the thiolate ligand and a vicinal tryptophan. Variations of the strength of this H-bond could provide a direct way to tune the stability along with the electronic and structural properties of NOS. We generated five different mutations of bsNOS Trp 66 , which can modulate this proximal H-bond. We investigated the effects of these mutations on different NOS complexes (Fe III , Fe II CO, and Fe II NO), using a combination of UV-visible absorption, EPR, FTIR, and resonance Raman spectroscopies. Our results indicate that (i) the proximal H-bond modulation can selectively decrease or increase the electron donating properties of the proximal thiolate, (ii) this modulation controls the -competition between distal and proximal ligands, (iii) this H-bond controls the stability of various NOS intermediates, and (iv) a fine tuning of the electron donation by the proximal ligand is required to allow at the same time oxygen activation and to prevent uncoupling reactions.

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Section: Role Of Tryptophan-thiolate H-bond In Bsnoscontrasting

confidence: 84%

mentioning

confidence: 63%

Section: Trpmentioning

confidence: 99%

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The Proximal Hydrogen Bond Network Modulates Bacillus subtilis Nitric-oxide Synthase Electronic and Structural Properties

Brunel

Wilson

Henry

et al. 2011

Journal of Biological Chemistry

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“…This new n 3 line displayed a frequency identical to that of the n 3 line of the Fe III NO complex (31). Additionally, the 1556 cm À1 (n 11 ) and 1575 cm À1 (n 2 ) lines of the Fe III NO complexes, which are not apparent in the resting Fe III spectrum, are observed in the spectrum of I435.…”

Section: Characterization By Resonance Raman Spectroscopy Of the Intementioning

confidence: 71%

“…Due to the large amount of protein required to carry out continuous-flow experiment (29), we used the bacterial NOS-like enzyme of Staphylococcus aureus (saNOS), which is well suited for those experiments and has been well characterized previously by steady-state and time-resolved resonance Raman spectroscopy (30,31). We first measured the apparent rate of PN decay achieved for iNOSoxy using this new model.…”

Section: Characterization By Resonance Raman Spectroscopy Of the Intementioning

confidence: 99%

Reaction Intermediates and Molecular Mechanism of Peroxynitrite Activation by NO Synthases

Lang

Maréchal

Couture

et al. 2016

Biophysical Journal

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The activation of the peroxynitrite anion (PN) by hemoproteins, which leads to its detoxification or, on the contrary to the enhancement of its cytotoxic activity, is a reaction of physiological importance that is still poorly understood. It has been known for some years that the reaction of hemoproteins, notably cytochrome P450, with PN leads to the buildup of an intermediate species with a Soret band at~435 nm (I435). The nature of this intermediate is, however, debated. On the one hand, I435 has been presented as a compound II species that can be photoactivated to compound I. A competing alternative involves the assignment of I435 to a ferric-nitrosyl species. Similar to cytochromes P450, the buildup of I435 occurs in nitric oxide synthases (NOSs) upon their reaction with excess PN. Interestingly, the NOS isoforms vary in their capacity to detoxify/activate PN, although they all show the buildup of I435. To better understand PN activation/detoxification by heme proteins, a definitive assignment of I435 is needed. Here we used a combination of fine kinetic analysis under specific conditions (pH, PN concentrations, and PN/NOSs ratios) to probe the formation of I435. These studies revealed that I435 is not formed upon homolytic cleavage of the O-O bond of PN, but instead arises from side reactions associated with excess PN. Characterization of I435 by resonance Raman spectroscopy allowed its identification as a ferric iron-nitrosyl complex. Our study indicates that the model used so far to depict PN interactions with hemo-thiolate proteins, i.e., leading to the formation and accumulation of compound II, needs to be reconsidered.

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

Santolini

2011

Journal of Inorganic Biochemistry

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Trp180 of endothelial NOS and Trp56 of bacterial saNOS modulate sigma bonding of the axial cysteine to the heme

Cited by 14 publications

References 64 publications

The Proximal Hydrogen Bond Network Modulates Bacillus subtilis Nitric-oxide Synthase Electronic and Structural Properties

The Proximal Hydrogen Bond Network Modulates Bacillus subtilis Nitric-oxide Synthase Electronic and Structural Properties

Reaction Intermediates and Molecular Mechanism of Peroxynitrite Activation by NO Synthases

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

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