7NBW
Crystal structure of PqsR (MvfR) ligand-binding domain in complex with a pyridin agonist
Summary for 7NBW
| Entry DOI | 10.2210/pdb7nbw/pdb |
| Descriptor | Transcriptional regulator MvfR, ~{N}-[3-(4-fluorophenyl)prop-2-ynyl]-2-(trifluoromethyl)pyridin-4-amine (3 entities in total) |
| Functional Keywords | quorum sensing, lysr-type transcriptional regulator, pseudomonas, 2 quinolone signaling system, lttr, dna binding protein |
| Biological source | Pseudomonas aeruginosa PAO1 |
| Total number of polymer chains | 1 |
| Total formula weight | 25994.31 |
| Authors | Schmelz, S.,Blankenfeldt, W. (deposition date: 2021-01-28, release date: 2021-10-06, Last modification date: 2024-01-31) |
| Primary citation | Schutz, C.,Hodzic, A.,Hamed, M.,Abdelsamie, A.S.,Kany, A.M.,Bauer, M.,Rohrig, T.,Schmelz, S.,Scrima, A.,Blankenfeldt, W.,Empting, M. Divergent synthesis and biological evaluation of 2-(trifluoromethyl)pyridines as virulence-attenuating inverse agonists targeting PqsR. Eur.J.Med.Chem., 226:113797-113797, 2021 Cited by PubMed Abstract: A short and divergent route towards new derivatives of 2-(trifluoromethyl)pyridines as potent inverse agonists of the bacterial target PqsR against Pseudomonas aeruginosa (PA) infections is described. This Gram-negative pathogen causes severe nosocomial infections and common antibiotic treatment options are rendered ineffective due to resistance issues. Based on an earlier identified optimized hit, we conducted derivatization and rigidification attempts employing two central building blocks. The western part of the molecule is built up via a 2-(trifluoromethyl)pyridine head group equipped with a terminal alkyne. The eastern section is then introduced through aryliode motifs exploiting Sonogashira as well as Suzuki-type chemistry. Subsequent modification provided quick access to an array of compounds, allowed for deep SAR insights, and enabled to optimize the hit scaffold into a lead structure of nanomolar potency combined with favorable in vitro ADME/T features. PubMed: 34520957DOI: 10.1016/j.ejmech.2021.113797 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.28 Å) |
Structure validation
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