Structure of the MurA-LpxC enzyme complex in modulating peptidoglycan and lipopolysaccharide biosynthesis.

Authors

Joshua Yi Yeo, Xin-Fu Yan, Zhu Qiao, Yan Yu Liew, Phong Hoa Do, Yuguang Mu, Yong-Gui Gao

Published in

Journal of structural biology. Pages 108374. Sep 19, 2026. Epub Sep 19, 2026.

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.

PMID:
42762934
Bibliographic data and abstract were imported from PubMed on 20 Sep 2026.

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