Summary for 9QOS
| Entry DOI | 10.2210/pdb9qos/pdb |
| Related | 9QMR |
| Descriptor | Aminoglycoside 3'-phosphotransferase, 5-chloranyl-4-(1~{H}-pyrazol-5-yl)-1~{H}-pyrrolo[2,3-b]pyridine (3 entities in total) |
| Functional Keywords | inhibitor, complex, enzyme, antibiotic |
| Biological source | Pseudomonas aeruginosa |
| Total number of polymer chains | 2 |
| Total formula weight | 64485.16 |
| Authors | Guichou, J.F.,Gelin, M.,Tomaszczyk, M.,Kowalewski, J.,Lionne, C. (deposition date: 2025-03-26, release date: 2026-02-11) |
| Primary citation | Kowalewski, J.,Deutscher, R.,Richardoz, M.,Tomaszczyk, M.,Gelin, M.,Labesse, G.,Hausch, F.,Wright, G.D.,Dunyach-Remy, C.,Guichou, J.F.,Lionne, C. Fragment-based drug design of a bacterial kinase inhibitor capable of increasing the antibiotic sensitivity of clinical isolates. Commun Chem, 8:417-417, 2025 Cited by PubMed Abstract: According to the World Health Organization (WHO), antimicrobial resistance is a serious global health issue. Overcoming antibiotic resistance involves several strategies, including the inhibition of resistance mechanisms. Among the various resistance mechanisms, aminoglycoside phosphotransferases (APHs) catalyze the transfer of the γ-phosphate from a nucleotide donor to various aminoglycosides, leading to their inactivation. In this work, using a fragment-based drug design (FBDD) approach, we have identified and characterized a promising APH inhibitor capable of increasing the sensitivity of Pseudomonas aeruginosa and Staphylococcus aureus resistant to aminoglycosides. It is therefore a good candidate for the future development of APH inhibitors to be prescribed in combination with aminoglycosides. This molecule is a competitive inhibitor of adenosine 5'-triphosphate (ATP), the phosphate donor of APHs. Further studies are required to optimize this molecule to improve its specificity for APHs and its bioavailability in bacteria. PubMed: 41310159DOI: 10.1038/s42004-025-01795-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.97 Å) |
Structure validation
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