MacP bypass variants of Streptococcus pneumoniae PBP2a suggest a conserved mechanism for the activation of bifunctional cell wall synthases.

Autor: Midonet C; Department of Microbiology, Harvard Medical School, Blavatnik Institute, Boston, Massachusetts, USA., Bisset S; Department of Molecular Biology, Umeå University, Umeå, Sweden., Shlosman I; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Blavatnik Institute, Boston, Massachusetts, USA., Cava F; Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Center for Microbial Research (UCMR), Umea, Sweden.; Department of Molecular Biology, Science for Life Laboratory (SciLifeLab), Umeå University, Umeå, Sweden., Rudner DZ; Department of Microbiology, Harvard Medical School, Blavatnik Institute, Boston, Massachusetts, USA., Bernhardt TG; Department of Microbiology, Harvard Medical School, Blavatnik Institute, Boston, Massachusetts, USA.; Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
Jazyk: angličtina
Zdroj: MBio [mBio] 2023 Dec 19; Vol. 14 (6), pp. e0239023. Date of Electronic Publication: 2023 Oct 17.
DOI: 10.1128/mbio.02390-23
Abstrakt: Importance: Class A penicillin-binding proteins (aPBPs) play critical roles in bacterial cell wall biogenesis. As the targets of penicillin, they are among the most important drug targets in history. Although the biochemical activities of these enzymes have been well studied, little is known about how they are regulated in cells to control when and where peptidoglycan is made. In this report, we isolate variants of the Streptococcus pneumoniae enzyme PBP2a that function in cells without MacP, a partner normally required for its activity. The amino acid substitutions activate the cell wall synthase activity of PBP2a, and their location in a model structure suggests an activation mechanism for this enzyme that is shared with aPBPs from distantly related organisms with distinct activators.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE