Hongnan Cao et al. present the X-ray crystal structure of E. coli dihydrofolate reductase (DHFR) in complex with its reduced substrate, (6s)-5,6,7,8-tetrahydrofolate (FH4). This structure provides the first glimpse of the rate-limiting product release step of the DHFR mechanism and suggests a strategy for designing DHFR-targeting antibiotics.
- Hongnan Cao
- Mu Gao
- Jeffrey Skolnick
