30NX

Cryo-EM structure of Acinetobacter baumannii LolDF bound to abaucin with lipoprotein

Summary for 30NX

• Entry DOI: 10.2210/pdb30nx/pdb
• EMDB information: 57887
• Descriptor: Lipoprotein-releasing system ATP-binding protein LolD, ABC transporter permease, 1'-[2-[4-(trifluoromethyl)phenyl]ethyl]spiro[1~{H}-3,1-benzoxazine-4,4'-piperidine]-2-one, ... (6 entities in total)
• Functional Keywords: loldf, /lipoprotein, /inhibition, / abaucin, transport protein
• Biological source: Acinetobacter baumannii; More
• Total number of polymer chains: 4
• Total formula weight: 140335.12

Authors

Dong, H.,Tang, X.,Pang, J.,Chen, Y.,ZeRang, Z. (deposition date: 2026-05-05, release date: 2026-11-04)

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

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: 42436156
DOI: 10.1038/s41467-026-75428-4

Experimental method

ELECTRON MICROSCOPY (3.38 Å)