Chemoselective Proteomics, Zinc Fingers, and a Zinc(II) Model for H 2 S Mediated Persulfidation.

The gasotransmitter hydrogen sulfide (H 2 S) is thought to be involved in the post-translational modification of cysteine residues to produce reactive persulfides. A persulfide-specific chemoselective proteomics approach with mammalian cells has identified a broad range of zinc finger (ZF) proteins as targets of persulfidation. Parallel studies with isolated ZFs show that persulfidation is mediated by Zn II , O 2 , and H 2 S, with intermediates involving oxygen- and sulfur-based radicals detected by mass spectrometry and optical spectroscopies. A small molecule Zn II complex exhibits analogous reactivity with H 2 S and O 2 , giving a persulfidated product. These data show that Zn II is not just a biological structural element, but also plays a critical role in mediating H 2 S-dependent persulfidation. ZF persulfidation appears to be a general post-translational modification and a possible conduit for H 2 S signaling. This work has implications for our understanding of H 2 S-mediated signaling and the regulation of ZFs in cellular physiology and development.