Summary information and primary citation
- PDB-id
- 6wpa; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- DNA binding protein-DNA
- Method
- X-ray (3.09 Å)
- Summary
- Structure of avar1 bound to DNA half-site
- Reference
- Kapoor I, Olivares P, Nair SK (2020): "Biochemical basis for the regulation of biosynthesis of antiparasitics by bacterial hormones." Elife, 9. doi: 10.7554/eLife.57824.
- Abstract
- Diffusible small molecule microbial hormones drastically alter the expression profiles of antibiotics and other drugs in actinobacteria. For example, avenolide (a butenolide) regulates production of avermectin, derivatives of which are used in the treatment of river blindness and other parasitic diseases. Butenolides and γ-butyrolactones control production of pharmaceutically important secondary metabolites by binding to TetR family transcriptional repressors. Here, we describe a concise, 22-step synthetic strategy for the production of avenolide. We present crystal structures of the butenolide receptor AvaR1 in isolation, and in complex with avenolide, as well as AvaR1 bound to an oligonucleotide derived from its operator. Biochemical studies guided by the co-crystal structures enable identification of 90 new actinobacteria that may be regulated by butenolides, two of which are experimentally verified. These studies provide a foundation for understanding regulation of microbial secondary metabolite production, which may be exploited for the discovery and production of novel medicines.
