25RW

Peptidoglycan and lipopolysaccharide biosynthesis enzymes with inhibitor

Summary for 25RW

• Entry DOI: 10.2210/pdb25rw/pdb
• EMDB information: 80332
• Descriptor: UDP-N-acetylglucosamine 1-carboxyvinyltransferase,UDP-3-O-acyl-N-acetylglucosamine deacetylase, N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-4-{[4-(morpholin-4-ylmethyl)phenyl]ethynyl}benzamide (2 entities in total)
• Functional Keywords: biogenesis, peptidoglycan synthesis enzyme, lipopolysaccharide synthesis enzyme, bacterial cell wall, bacterial outer membrane, biosynthetic protein
• Biological source: Pseudomonas aeruginosa PAO1; More
• Total number of polymer chains: 2
• Total formula weight: 156736.68

Authors

Yeo, J.Y.,Yan, X.F.,Gao, Y.G. (deposition date: 2026-04-16, release date: 2026-09-30)

Primary citation

Yeo, J.Y.,Yan, X.F.,Qiao, Z.,Liew, Y.Y.,Do, P.H.,Mu, Y.,Gao, Y.G.
Structure of the MurA-LpxC enzyme complex in modulating peptidoglycan and lipopolysaccharide biosynthesis.
J.Struct.Biol., :108374-108374, 2026

PubMed Abstract: Coordination of peptidoglycan and lipopolysaccharide biosynthesis is essential for maintaining Gram-negative cell envelope homeostasis. Two enzymes, MurA and LpxC, catalyze the first committed steps in peptidoglycan and lipopolysaccharide biosynthesis, respectively. Here, we determined cryo-electron microscopy (cryo-EM) structures of the Pseudomonas aeruginosa MurA-LpxC complex in the absence and presence of the LpxC inhibitor CHIR-090, providing molecular insights into complex formation. Structure-guided mutagenesis of MurA, together with in vitro pull-down assays, identified residues crucial for complex formation. We show that MurA G58 favors, but is not sufficient for complex formation, as substitution of this residue to mimic Escherichia coli MurA (G58S) weakens the interaction. Together, our study advances our structural understanding of how two biosynthesis pathways for peptidoglycan and lipopolysaccharide are coordinated to maintain a synergistic and balanced cell envelope.

PubMed: 42762934
DOI: 10.1016/j.jsb.2026.108374

Experimental method

ELECTRON MICROSCOPY (2.35 Å)