4nyg | pdb_00004nyg

Crystal structure of the E. coli thiM riboswitch in complex with thiamine

spinqualitylabelsall models 4nyg, resolution 3.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4nyg is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.05Å Ligands: A23, MG, VIB Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Thiamine pyrophosphate (TPP) riboswitches regulate essential genes in bacteria by changing conformation upon binding intracellular TPP. Previous studies using fragment-based approaches identified small molecule "fragments" that bind this gene-regulatory mRNA domain. Crystallographic studies now show that, despite having micromolar Kds, four different fragments bind the TPP riboswitch site-specifically, occupying the pocket that recognizes the aminopyrimidine of TPP. Unexpectedly, the unoccupied site that would recognize the pyrophosphate of TPP rearranges into a structure distinct from that of the cognate complex. This idiosyncratic fragment-induced conformation, also characterized by small-angle X-ray scattering and chemical probing, represents a possible mechanism for adventitious ligand discrimination by the riboswitch, and suggests that off-pathway conformations of RNAs can be targeted for drug development. Our structures, together with previous screening studies, demonstrate the feasibility of fragment-based drug discovery against RNA targets. Validating Fragment-Based Drug Discovery for Biological RNAs: Lead Fragments Bind and Remodel the TPP Riboswitch Specifically.,Warner KD, Homan P, Weeks KM, Smith AG, Abell C, Ferre-D'Amare AR Chem Biol. 2014 May 22;21(5):591-5. doi: 10.1016/j.chembiol.2014.03.007. Epub, 2014 Apr 24. PMID:24768306 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Riboswitch 3D structures

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