Direct Zinc Finger Protein Persulfidation by H<sub>2</sub>S Is Facilitated by Zn<sup>2+</sup>

Lange, M.; Ok, Kiwon; Shimberg, Geoffrey D.; Bursać, Biljana; Markó, Lajos; Michel, Sarah L. J.; Filipovic, Milos R.

doi:10.1002/ange.201900823

Cited by 11 publications

(6 citation statements)

References 35 publications

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“…We speculate that sulfane sulfur is a key component of such a "zinc redox switch", enabling it to provide high-affinity for zinc and protection against excess oxidative/electrophilic stress. Supporting our notion, zinc finger proteins such as tristetraprolin (47), androgen receptor (48), and prolyl hydroxylase (49) were reported to undergo persulfidation by H 2 S. In this context, H 2 S inhibits enzymatic activity of tristetraprolin and androgen receptor, but increases enzymatic activity of prolyl hydroxylase. A possible explanation for this difference is that excess exogenous H 2 S may cause protein polysulfidation, thereby disturbing the native protein structure.…”

Section: Discussionsupporting

confidence: 57%

Growth inhibitory factor/metallothionein-3 is a sulfane sulfur-binding protein

Shinkai,

Ding,

Matsui

et al. 2023

Preprint

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Cysteine-bound sulfane sulfur atoms in proteins have received much attention as key factors in cellular redox homeostasis. However, the role of sulfane sulfur in zinc regulation has been overlooked. We report here that cysteine-bound sulfane sulfur atoms serve as ligands to hold and release zinc ions in growth inhibitory factor (GIF)/metallothionein-3 (MT3) with an unexpected C-S-S-Zn structure. Oxidation of such a zinc/persulfide cluster in Zn7GIF/MT3 results in the release of zinc ions, and intramolecular tetrasulfide bridges in apo-GIF/MT3 efficiently undergo S-S bond cleavage by thioredoxin to regenerate Zn7GIF/MT3. Three-dimensional molecular modeling confirmed the critical role of the persulfide group in the thermostability and Zn-binding affinity of GIF/MT3. The present discovery raises the fascinating possibility that the function of other Zn-binding proteins is controlled by sulfane sulfur.

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Section: Discussionsupporting

confidence: 57%

Growth inhibitory factor/metallothionein-3 is a sulfane sulfur-binding protein

Shinkai,

Ding,

Matsui

et al. 2023

Preprint

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“…This protective effect of RNA on the zinc sites/reactivity of Zn II 2 ‐TTP‐2D was also observed in studies performed by our laboratory that examined the reactivity of the signaling molecule H 2 S with TTP. We found that H 2 S modifies Zn II 2 ‐TTP‐2D alone, but does not react with Zn II 2 ‐TTP‐2D/RNA . In contrast, we have also reported that Cu I Cl disrupts the Zn II 2 ‐TTP‐2D/RNA complex .…”

Section: Discussionmentioning

confidence: 61%

Role of Gold in Inflammation and Tristetraprolin Activity

Neu

et al. 2020

Chemistry A European J

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The zinc finger protein tristetraprolin (TTP) regulates inflammation by downregulatingc ytokinem RNAs. Misregulation resultsi na rthritis, sepsis and cancer,a nd there is an interesti nm odulating TTP activity with exogenous agents. Gold hasa nti-inflammatory properties and has recently been shown to modulate the signaling pathway that produces TTP,s uggesting that TTP may be at arget of gold. The reactivity of [Au III (terpy)Cl]Cl 2 with TTPw as investigated by UV/Vis spectroscopy,s pin-filter inductively coupled plasma mass spectrometry,X -ray absorption spectroscopy and native electrospray ionization mass spectrometry.A u III was found to replace zinc in the protein active site in the reduced Au I form, with the Au I ion coordinated to two cysteine residues in al inear geometry.T he replacement of Zn II with Au I resultsi nl oss of both secondary structure and RNA binding function. In contrast, when Zn II TTP is boundt oi ts RNA target, no replacement of Zn II with Au I is observed, even in the presence of excessA u III terpy.T his discovery of differential reactivity of gold with TTP versus TTP/RNA offers ap otentials trategy for selectivet argeting with gold complexest oc ontroli nflammation.Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.org/10.1002/chem.201904837.Scheme1.Cartoon diagram of role of TTP in TNF-a signaling. TTP (in yellow) regulates TNF-a by binding to and degrading its mRNA as part of the NF-kBs ignaling pathway.

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“…[56][57][58] In addition to the Cu-oxido, Cu-nitrene compounds 59,60 as well as zinc-based proteins have been studied with Cryo-ESI. 61 Alternative MS setups to analyze active intermediates…”

Section: Paper Dalton Transactionsmentioning

confidence: 99%

“…56–58 In addition to the Cu-oxido, Cu-nitrene compounds 59,60 as well as zinc-based proteins have been studied with Cryo-ESI. 61…”

Section: Esi-ms For the Characterization Of Reactive Intermediatesmentioning

confidence: 99%