Throwing a monkey wrench in the motor: targeting DExH/D box proteins with small molecule inhibitors

DExH/D box proteins are molecular motors that utilize the energy derived from NTP hydrolysis to perform work - from helicases that remodel RNA to RNPases that alter RNA-protein complexes. Members of this class of proteins are uniquely placed along the RNA information highway to regulate the flow of genetic information. They have been implicated in a number of nodal points encompassing nuclear, cytoplasmic, and organellar RNA-based processes. The identification and characterization of three unique natural products that selectively inhibit the activity of eukaryotic initiation factor (eIF)4A (DDX2) has provided proof-of-principle that the activity of DExH/D box family members can be selectively targeted. Extending these achievements to other DExH/D box proteins is an important future challenge for drugging this family of proteins. This article is part of a Special Issue entitled: The Biology of RNA helicases - Modulation for life.