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TitleStructural, functional, and mechanistic studies of the bacterial divisome FtsWIQBL in complex with antibiotics.
Journal, issue, pagesStructure, Year 2026
Publish dateJul 31, 2026
AuthorsShimin Zhu / Yanjie Hu / Rong Wang / Danyang Li / Zhengyu Zhang / Changjiang Dong /
PubMed AbstractSeptal peptidoglycan (sPG) biosynthesis during bacterial cell division is driven by the dynamic divisome complex. Its core components, glycosyltransferase FtsW and transpeptidase FtsI are responsible ...Septal peptidoglycan (sPG) biosynthesis during bacterial cell division is driven by the dynamic divisome complex. Its core components, glycosyltransferase FtsW and transpeptidase FtsI are responsible for glycan chain polymerization and crosslinking, respectively. FtsI is also the target of β-lactams. The essential membrane complex FtsQ-FtsB-FtsL regulates FtsWI enzymatic activity. However, the mechanism of FtsQBLWI-mediated sPG synthesis and β-lactam-induced conformational changes have remained elusive. Here, we present cryo-electron microscopy (cryo-EM) structures of the Pseudomonas aeruginosa FtsQBLWI complex in the apo state and bound to aztreonam or imipenem. Our work reveals intricate structural details, including the putative substrate-binding cavities of FtsW, FtsI-mediated allosteric activation of FtsW, and β-lactam-triggered conformational rearrangements. Collectively, these structural, genetic and biochemical analyses reveal the mechanism of FtsQBLWI-controlled sPG synthesis and β-lactam action on this complex, providing a molecular basis for optimizing existing β-lactams and developing novel antibiotics.
External linksStructure / PubMed:42537644
MethodsEM (single particle)
Resolution3.12 - 3.6 Å
Structure data

EMDB-80113, PDB-25hr:
Cryo-EM structure of Pseudomonas aeruginosa FtsQBLWI in complex with imipenem
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-80118, PDB-25hs:
Cryo-EM structure of Pseudomonas aeruginosa FtsQBLWI in complex with aztreonam
Method: EM (single particle) / Resolution: 3.12 Å

EMDB-80125, PDB-25hw:
Cryo-EM structure of Pseudomonas aeruginosa FtsQBLWI
Method: EM (single particle) / Resolution: 3.28 Å

Chemicals

PDB-1h3n:
Leucyl-tRNA synthetase from Thermus thermophilus complexed with a sulphamoyl analogue of leucyl-adenylate

ChemComp-AZR:
2-({[(1Z)-1-(2-amino-1,3-thiazol-4-yl)-2-oxo-2-{[(2S,3S)-1-oxo-3-(sulfoamino)butan-2-yl]amino}ethylidene]amino}oxy)-2-methylpropanoic acid

Source
  • pseudomonas aeruginosa pao1 (bacteria)
KeywordsANTIBIOTIC / core divisome / peptidoglycan D / D-transpeptidase / imipenem / aztreonam / STRUCTURAL PROTEIN / Pseudomonas aeruginosa

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