Chemogenetic Manipulation of H₂S with Spatiotemporal Precision.

ABSTRACT: Hydrogen sulfide (H₂S) is a signaling molecule with a plethora of biological functions, yet precision tools for modulating its intracellular flux remain scarce. Conventional small-molecule donors and enzymatic systems often suffer from off-target reactivity, uncontrolled release kinetics, and redox crosstalk, confounding mechanistic studies. Here, we establish a Salmonella typhimurium d-cysteine desulfhydrase (stDCyD)-derived chemogenetic tool for controlled H₂S manipulation in living cells. stDCyD catalyzes the α,β-elimination of d-cysteine to selectively yield bioavailable H₂S. We term this tool H₂SWITCH. Our approach exhibits pronounced enantioselectivity for d-cysteine, robust catalytic efficiency at physiological temperatures, and tem

SUBMITTER: Ghaffari Zaki A 

PROVIDER: S-EPMC12848812 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature