A structural biology perspective on bioactive small molecules and their plant targets

Structural biology efforts in recent years have generated numerous co-crystal structures of bioactive small molecules interacting with their plant targets. These studies include the targets of various phytohormones, pathogen-derived effectors, herbicides and other bioactive compounds. Here we discuss that this collection of structures contains excellent examples of nine collective observations: molecular glues, allostery, inhibitors, molecular mimicry, promiscuous binding sites, unexpected electron densities, natural selection at atomic resolution, and applications in structure-guided mutagenesis and small molecule design.

► Over 70 crystal structures of plant proteins with bioactive small molecules have been reported. ► We discuss nine collective observations from these manuscripts. ► We found clear examples of small molecules acting as inhibitors, allosteric ligands, or molecular glues. ► Small molecules can also mimic endogenous molecules or bind to promiscuous binding sites. ► Unexpected electron densities have revealed surprising ligands. ► Structural biology on herbicide targets explain resistance mutations. ► Structural information has been used for small molecule design and structure-guided mutagenesis.