9R24
Cryo-EM structure of Acinetobacter baumannii LolDF bound abaucin (narrow cavity)
Summary for 9R24
| Entry DOI | 10.2210/pdb9r24/pdb |
| EMDB information | 53522 |
| Descriptor | Lipoprotein-releasing system transmembrane subunit LolC, Lipoprotein-releasing system ATP-binding protein LolD, 1'-[2-[4-(trifluoromethyl)phenyl]ethyl]spiro[1~{H}-3,1-benzoxazine-4,4'-piperidine]-2-one, ... (5 entities in total) |
| Functional Keywords | loldf, /abaucin, /inhibitor, /narrow cavity, transport protein |
| Biological source | Acinetobacter baumannii More |
| Total number of polymer chains | 4 |
| Total formula weight | 140600.96 |
| Authors | |
| Primary citation | Pang, J.,Chen, Y.,Zhou, D.,Wang, L.,Xiao, Y.,Zhang, Z.,Zerang, Z.,Duan, M.,Zhang, L.,Gu, X.,Xiao, M.,Wang, J.,Cui, H.,Wen, A.,Zhang, S.,Zhang, Y.,Ying, B.,Ouyang, L.,Wei, X.,Ding, B.S.,Tang, X.,Dong, H. Conformational hijacking of lipoprotein transporter LolDF enables precision antimicrobial activity against Acinetobacter baumannii. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: Acinetobacter baumannii is a critical-priority pathogen with increasing antibiotic resistance. Here, we define the mechanism of abaucin, a first-in-class narrow-spectrum antibiotic that selectively targets A. baumannii by inhibiting its essential lipoprotein transporter, LolDF. Extending prior studies of archived strains, we demonstrate potent activity against clinically isolated carbapenem-resistant A. baumannii (CRAB) strains both in vitro and in a murine pneumonia model. Cryo-EM structures of abaucin-bound LolDF reveal symmetric binding of two abaucin molecules within the LolDF cavity, which lock the transporter in a non-productive, outward-open conformation. Biochemical and structural analyses show that abaucin does not block substrate binding but instead traps the substrate-loaded transporter and prevents transfer to LolA. Together, these findings uncover a unique symmetry-enabled conformation-hijacking mechanism and establish LolDF as a tractable target for precision antibiotic development. PubMed: 42436156DOI: 10.1038/s41467-026-75428-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.15 Å) |
Structure validation
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