9E50
TAD from Carmabin Biosynthetic Pathway in complex with NAD - Crystal Form 2
Summary for 9E50
| Entry DOI | 10.2210/pdb9e50/pdb |
| Related | 9E4S 9E4U 9E4X |
| Descriptor | Amino acid adenylation domain protein, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, IODIDE ION, ... (4 entities in total) |
| Functional Keywords | nad-binding, biosynthetic protein |
| Biological source | Moorena producens 3L |
| Total number of polymer chains | 2 |
| Total formula weight | 90482.53 |
| Authors | Rankin, M.R.,Smith, J.L. (deposition date: 2024-10-26, release date: 2025-02-26, Last modification date: 2025-09-24) |
| Primary citation | Olenginski, L.T.,Wierzba, A.J.,Laursen, S.P.,Batey, R.T. Designing small molecules targeting a cryptic RNA binding site through base displacement. Nat.Chem.Biol., 2025 Cited by PubMed Abstract: Most RNA-binding small molecules have limited solubility, weak affinity and/or lack of specificity, restricting the medicinal chemistry often required for lead compound discovery. We reasoned that conjugation of these unfavorable ligands to a suitable 'host' molecule can solubilize the 'guest' and deliver it site-specifically to an RNA of interest to resolve these issues. Using this framework, we designed a small-molecule library that was hosted by cobalamin (Cbl) to interact with the Cbl riboswitch through a common base displacement mechanism. Combining in vitro binding, cell-based assays, chemoinformatic modeling and structure-based design, we unmasked a cryptic binding site within the riboswitch that was exploited to discover compounds that have affinity exceeding the native ligand, antagonize riboswitch function or bear no resemblance to Cbl. These data demonstrate how a privileged biphenyl-like scaffold effectively targets RNA by optimizing π-stacking interactions within the binding pocket. PubMed: 40883492DOI: 10.1038/s41589-025-02018-8 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.68 Å) |
Structure validation
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