ArticleProceedings of the National Academy of Sciences of the United States of America2016
Cofactor bypass variants reveal a conformational control mechanism governing cell wall polymerase activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 42 citations in OpenAlex.
- Enzymatic activity of PBP1B is required for growth rate-independent ppGpp-mediated resistance to PBP2 inhibitors inJournal of bacteriology · 2026Article
- Molecular dissection of Class A PBP function uncovers novel features of the non-canonical Clostridioides difficile divisome complex.PLoS genetics · 2025Article
- The hit-and-run of cell wall synthesis: LpoB transiently binds and activates PBP1b through a conserved allosteric switch.Nature communications · 2025Article
- Molecular dissection of Class A PBP function uncovers novel features of the non-canonicalbioRxiv : the preprint server for biology · 2025Article
- Synthesis of lipid-linked precursors of the bacterial cell wall is governed by a feedback control mechanism in Pseudomonas aeruginosa.Nature microbiology · 2024Article
- Allosteric activation of cell wall synthesis during bacterial growth.Nature communications · 2023Article
- The Influence of Outer Membrane Protein on Ampicillin Resistance ofThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2023Article
- What Is Motion? Recent Advances in the Study of Molecular Movement Patterns of the Peptidoglycan Synthesis Machines.Journal of bacteriology · 2022Review
- Structural diversity, bioactivity, and biosynthesis of phosphoglycolipid family antibiotics: Recent advances.BBA advances · 2022Article
- The Tol-Pal System Plays an Important Role in Maintaining Cell Integrity During Elongation inFrontiers in microbiology · 2022Article
- The LpoA activator is required to stimulate the peptidoglycan polymerase activity of its cognate cell wall synthase PBP1a.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- MltG activity antagonizes cell wall synthesis by both types of peptidoglycan polymerases in Escherichia coli.Molecular microbiology · 2021Article
- Peptidoglycan: Structure, Synthesis, and Regulation.EcoSal Plus · 2021Article
- Review
- Regulation of peptidoglycan synthesis and remodelling.Nature reviews. Microbiology · 2020Review
- Structure of the Peptidoglycan Synthase Activator LpoP in Pseudomonas aeruginosa.Structure (London, England : 1993) · 2020Article
- Class-A penicillin binding proteins do not contribute to cell shape but repair cell-wall defects.eLife · 2020Article
- Simultaneously inhibiting undecaprenyl phosphate production and peptidoglycan synthases promotes rapid lysis in Escherichia coli.Molecular microbiology · 2019Article
- Identification of Genes Involved in Biogenesis of Outer Membrane Vesicles (OMVs) inFrontiers in microbiology · 2019Article
- Induced conformational changes activate the peptidoglycan synthase PBP1B.Molecular microbiology · 2018Article
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7 authors at 1 institution in 1 country.
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Abstract
To fortify their cytoplasmic membrane and protect it from osmotic rupture, most bacteria surround themselves with a peptidoglycan (PG) exoskeleton synthesized by the penicillin-binding proteins (PBPs). As their name implies, these proteins are the targets of penicillin and related antibiotics. We and others have shown that the PG synthases PBP1b and PBP1a of Escherichia coli require the outer membrane lipoproteins LpoA and LpoB, respectively, for their in vivo function. Although it has been demonstrated that LpoB activates the PG polymerization activity of PBP1b in vitro, the mechanism of activation and its physiological relevance have remained unclear. We therefore selected for variants of PBP1b (PBP1b*) that bypass the LpoB requirement for in vivo function, reasoning that they would shed light on LpoB function and its activation mechanism. Several of these PBP1b variants were isolated and displayed elevated polymerization activity in vitro, indicating that the activation of glycan polymer growth is indeed one of the relevant functions of LpoB in vivo. Moreover, the location of amino acid substitutions causing the bypass phenotype on the PBP1b structure support a model in which polymerization activation proceeds via the induction of a conformational change in PBP1b initiated by LpoB binding to its UB2H domain, followed by its transmission to the glycosyl transferase active site. Finally, phenotypic analysis of strains carrying a PBP1b* variant revealed that the PBP1b-LpoB complex is most likely not providing an important physical link between the inner and outer membranes at the division site, as has been previously proposed.
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