2011
DOI: 10.1038/nm.2405
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Host S-nitrosylation inhibits clostridial small molecule–activated glucosylating toxins

Abstract: The global prevalence of severe Clostridium difficile infection highlights the profound clinical significance of clostridial glucosylating toxins1–4. Virulence is dependent on the autoactivation of a toxin cysteine protease5–9, which is promoted by the allosteric cofactor inositol hexakisphosphate (InsP6)10–17. Host mechanisms that protect against such exotoxins are poorly understood. It is increasingly appreciated that the pleiotropic functions attributed to nitric oxide (NO), including host immunity, are in … Show more

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Cited by 82 publications
(92 citation statements)
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“…important criterion for S-nitrosation specificity (43), and this has been demonstrated for several proteins (4,48). GSNO has been co-crystallized with GSTP1-1, prompting the proposal that GSNO binding precedes Cys 47 nitrosation (23).…”
Section: Discussionmentioning
confidence: 87%
See 2 more Smart Citations
“…important criterion for S-nitrosation specificity (43), and this has been demonstrated for several proteins (4,48). GSNO has been co-crystallized with GSTP1-1, prompting the proposal that GSNO binding precedes Cys 47 nitrosation (23).…”
Section: Discussionmentioning
confidence: 87%
“…Recently, protein S-nitrosation has emerged as an important cellular signaling mechanism, with a broad range of targets (37, 1) and significant implications for human health (6,4). Unlike other physiologically important post-translational modifications (e.g.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Cathelicidin and defensins have been shown to significantly reduce tissue damage and inflammation caused by TcdA and TcdB and reduce inflammatory cytokine production [Hing et al 2012;Giesemann et al 2008]. Another mechanism by which the host is able to affect the cytotoxicity of TcdA and TcdB is by direct chemical attenuation through S-nitrosylation that inhibits toxin cleavage and cell entry [Savidge et al 2011]. Attenuation of toxin activity was shown to be enhanced by addition of InsP 6 , highlighting a role for this cofactor in augmenting the antitoxin activity of S-nitrosylation [Savidge et al 2011].…”
Section: Role Of the Innate Immune Response Inmentioning
confidence: 99%
“…Another mechanism by which the host is able to affect the cytotoxicity of TcdA and TcdB is by direct chemical attenuation through S-nitrosylation that inhibits toxin cleavage and cell entry [Savidge et al 2011]. Attenuation of toxin activity was shown to be enhanced by addition of InsP 6 , highlighting a role for this cofactor in augmenting the antitoxin activity of S-nitrosylation [Savidge et al 2011].…”
Section: Role Of the Innate Immune Response Inmentioning
confidence: 99%