Folding to self-destruct

Abstract

Protein Folding The bacterial enzyme glucosamine-6-phosphate synthase (GlmS) is essential for synthesis of the cell wall. Its expression is regulated by a structured messenger RNA (mRNA) element, the glmS riboswitch. Most riboswitches are stabilized in an “on” conformational state by binding a ligand. In GlmS, however, ligand binding leads to self-cleavage, and this, in turn, targets the mRNA for degradation. Savinov and Block used optical tweezers to measure folding dynamics and cleavage rates for the core glmS ribozyme with and without ligand. A specific duplex called P2.2 folds last and transiently. Ligand binding does not stabilize the P2.2 duplex; it is only when ligand binds this structure that cleavage occurs. A compound that stabilizes the duplex could make an antibiotic candidate. Proc. Natl. Acad. Sci. U.S.A. 115 , 11976 (2018).