Summary information and primary citation
- PDB-id
-
5kx9;
DSSR-derived features in text and
JSON formats
- Class
- RNA-inhibitor
- Method
- X-ray (2.9 Å)
- Summary
- Selective small molecule inhibition of the fmn
riboswitch
- Reference
-
Howe JA, Xiao L, Fischmann TO, Wang H, Tang H, Villafania
A, Zhang R, Barbieri CM, Roemer T (2016): "Atomic
resolution mechanistic studies of ribocil: A highly
selective unnatural ligand mimic of the E. coli FMN
riboswitch." Rna Biol., 13,
946-954. doi: 10.1080/15476286.2016.1216304.
- Abstract
- Bacterial riboswitches are non-coding RNA structural
elements that direct gene expression in numerous metabolic
pathways. The key regulatory roles of riboswitches, and the
urgent need for new classes of antibiotics to treat
multi-drug resistant bacteria, has led to efforts to
develop small-molecules that mimic natural riboswitch
ligands to inhibit metabolic pathways and bacterial growth.
Recently, we reported the results of a phenotypic screen
targeting the riboflavin biosynthesis pathway in the
Gram-negative bacteria Escherichia coli that led to the
identification of ribocil, a small molecule inhibitor of
the flavin mononucleotide (FMN) riboswitch controlling
expression of this biosynthetic pathway. Although ribocil
is structurally distinct from FMN, ribocil functions as a
potent and highly selective synthetic mimic of the natural
ligand to repress riboswitch-mediated ribB gene expression
and inhibit bacterial growth both in vitro and in vivo.
Herein, we expand our analysis of ribocil; including mode
of binding in the FMN binding pocket of the riboswitch,
mechanisms of resistance and structure-activity
relationship guided efforts to generate more potent
analogs.
