Recently featured on the cover of Nature was ribocil, a new synthetic modulator of an essential bacterial pathway, reported by Merck Research Laboratories of Kenilworth, New Jersey. Merck is a member of the Industrial Macromolecular Crystallography Association (IMCA). Scientists explored the interaction of ribocil with its target, the flavin mononucleotide riboswitch, in part by proprietary research conducted at the Industrial Macromolecular Crystallography Association Collaborative Access Team (IMCA-CAT) X-ray beamline at the U.S. Department of Energy's Argonne National Laboratory, Advanced Photon Source.
From the cover caption: "The urgent need for new antibiotics is well recognized. Terry Roemer and colleagues at Merck now describe a new synthetic antibiotic, directed against a bacterial riboswitch. Riboswitches are stretches of non-coding RNA (ncRNA) whose structure is affected by a ligand — usually one related to the function of the protein encoded by the riboswitch-containing gene. The new drug, ribocil, blocks the flavin mononucleotide riboswitch-mediated expression of the ribB gene required for riboflavin biosynthesis. Ribocil inhibits bacterial cell growth and is effective in treating a bacterial infection in a mouse model."
Thomas Hermann in a News and Views feature in the same issue notes "By binding to the same ncRNA target (as flavin mononucleotide), ribocil tricks the riboswitch to respond, shutting off riboflavin production and depriving the bacteria of the essential metabolite. As a compelling piece of evidence, the researchers used X-ray crystallography to provide a snapshot of ribocil in the act of binding to the riboswitch RNA. Such structural information will be valuable for improving the antibacterial activity of ribocil derivatives for potential clinical use."
Read more:
- Nature: News and Views
- Research publication:
Howe, JA, et al. Selective small-molecule inhibition of an RNA structural element.
Nature 526, 672-677 (2015)
This research used resources at the Industrial Macromolecular Crystallography Association Collaborative Access Team (IMCA-CAT) beamline 17-ID, supported by the companies of the Industrial Macromolecular Crystallography Association through a contract with Hauptman-Woodward Medical Research Institute.
This research used resources at the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.