Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, MD, 21201, USA.
Department of Chemistry, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD, 21218, USA.
Angew Chem Int Ed Engl. 2024 Jul 1;63(27):e202401003. doi: 10.1002/anie.202401003. Epub 2024 May 29.
The gasotransmitter hydrogen sulfide (HS) 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, O, and HS, with intermediates involving oxygen- and sulfur-based radicals detected by mass spectrometry and optical spectroscopies. A small molecule Zn complex exhibits analogous reactivity with HS and O, giving a persulfidated product. These data show that Zn is not just a biological structural element, but also plays a critical role in mediating HS-dependent persulfidation. ZF persulfidation appears to be a general post-translational modification and a possible conduit for HS signaling. This work has implications for our understanding of HS-mediated signaling and the regulation of ZFs in cellular physiology and development.
气体递质硫化氢（HS）被认为参与半胱氨酸残基的翻译后修饰，以产生反应性过硫化物。一种具有哺乳动物细胞的过硫化物特异性化学选择性蛋白质组学方法已经鉴定出广泛的锌指（ZF）蛋白作为过硫化物的靶标。与分离的 ZF 的平行研究表明，过硫化物是由 Zn、O 和 HS 介导的，通过质谱和光学光谱检测到涉及氧和硫基自由基的中间体。小分子 Zn 配合物与 HS 和 O 表现出类似的反应性，生成过硫化物产物。这些数据表明，Zn 不仅是生物结构元素，而且在介导 HS 依赖性过硫化物中也起着关键作用。ZF 过硫化物似乎是一种普遍的翻译后修饰，也是 HS 信号传导的可能途径。这项工作对于我们理解 HS 介导的信号传导以及 ZF 在细胞生理学和发育中的调节具有重要意义。
