Longevity & AgingBacterial Enzyme ApaH Decaps RNA Stress Signals Using Two Binding Orientations
Scientists have mapped the precise molecular mechanism by which the bacterial enzyme ApaH removes 'alarmone' caps from RNA molecules. These Np4 caps accumulate on bacterial transcripts during stress and influence gene expression and RNA lifespan. Using X-ray crystallography, biochemical assays, and molecular dynamics simulations, the team showed that ApaH can bind its substrate in two alternative orientations due to a combination of non-specific and semi-specific recognition. Despite this flexibility, the enzyme efficiently decaps diverse RNA types. Critically, the enzyme's ability to accommodate substrates in two orientations means that inhibitors designed to mimic the substrate in one orientation may be bypassed when the substrate flips — a key consideration for antibiotic drug design targeting ApaH.
