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TitleStructure of the MurA-LpxC enzyme complex in modulating peptidoglycan and lipopolysaccharide biosynthesis.
Journal, issue, pagesJ Struct Biol, Vol. 218, Issue 4, Page 108374, Year 2026
Publish dateSep 19, 2026
AuthorsJoshua Yi Yeo / Xin-Fu Yan / Zhu Qiao / Yan Yu Liew / Phong Hoa Do / Yuguang Mu / Yong-Gui Gao /
PubMed AbstractCoordination of peptidoglycan and lipopolysaccharide biosynthesis is essential for maintaining Gram-negative cell envelope homeostasis. Two enzymes, MurA and LpxC, catalyze the first committed steps ...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.
External linksJ Struct Biol / PubMed:42762934
MethodsEM (single particle)
Resolution2.35 - 2.46 Å
Structure data

80331

25rv

EMDB-80331, PDB-25rv:
Structure of MurA in complex with ligand-bound LpxC
Method: EM (single particle) / Resolution: 2.46 Å

80332

25rw

EMDB-80332, PDB-25rw:
Peptidoglycan and lipopolysaccharide biosynthesis enzymes with inhibitor
Method: EM (single particle) / Resolution: 2.35 Å

Chemicals

ChemComp-MYR:
MYRISTIC ACID

ChemComp-C90:
N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-4-{[4-(morpholin-4-ylmethyl)phenyl]ethynyl}benzamide

Source
  • pseudomonas aeruginosa pao1 (bacteria)
KeywordsBIOSYNTHETIC PROTEIN / biogenesis / peptidoglycan synthesis enzyme / lipopolysaccharide synthesis enzyme / bacterial cell wall / bacterial outer membrane

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