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The MurG glycosyltransferase provides an oligomeric scaffold for the cytoplasmic steps of peptidoglycan biosynthesis in the human pathogen Bordetella pertussis
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-17 (2019), Scientific Reports, Scientific Reports, Nature Publishing Group, 2019, 9 (1), pp.4656. ⟨10.1038/s41598-019-40966-z⟩, 'Scientific Reports ', vol: 9, pages: 4656-14656-17 (2019), Scientific Reports, 2019, 9 (1), pp.4656. ⟨10.1038/s41598-019-40966-z⟩
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
Abstract
- Peptidoglycan is a major component of the bacterial cell wall and thus a major determinant of cell shape. Its biosynthesis is initiated by several sequential reactions catalyzed by cytoplasmic Mur enzymes. Mur ligases (MurC, -D, -E, and -F) are essential for bacteria, metabolize molecules not present in eukaryotes, and are structurally and biochemically tractable. However, although many Mur inhibitors have been developed, few have shown promising antibacterial activity, prompting the hypothesis that within the cytoplasm, Mur enzymes could exist as a complex whose architecture limits access of small molecules to their active sites. This suggestion is supported by the observation that in many bacteria, mur genes are present in a single operon, and pairs of these genes often are fused to generate a single polypeptide. Here, we explored this genetic arrangement in the human pathogen Bordetella pertussis and show that MurE and MurF are expressed as a single, bifunctional protein. EM, small angle X-ray scattering (SAXS), and analytical centrifugation (AUC) revealed that the MurE–MurF fusion displays an elongated, flexible structure that can dimerize. Moreover, MurE–MurF interacted with the peripheral glycosyltransferase MurG, which formed discrete oligomers resembling 4- or 5-armed stars in EM images. The oligomeric structure of MurG may allow it to play a bona fide scaffolding role for a potential Mur complex, facilitating the efficient conveyance of peptidoglycan-building blocks toward the inner membrane leaflet. Our findings shed light on the structural determinants of a peptidoglycan formation complex involving Mur enzymes in bacterial cell wall formation.
- Subjects :
- 0301 basic medicine
Cytoplasm
Operon
lcsh:Medicine
Peptidoglycan
N-Acetylglucosaminyltransferases
Bordetella pertussis
Article
Bacterial cell structure
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Bacterial Proteins
X-Ray Diffraction
Biosynthesis
Cell Wall
Catalytic Domain
Scattering, Small Angle
Glycosyltransferase
Humans
Inner membrane
Peptide Synthases
lcsh:Science
chemistry.chemical_classification
Binding Sites
Multidisciplinary
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
biology
lcsh:R
Glycosyltransferases
Anti-Bacterial Agents
Cell biology
030104 developmental biology
Enzyme
chemistry
biology.protein
lcsh:Q
030217 neurology & neurosurgery
Bacterial Outer Membrane Proteins
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....10af612b281163bdc6fd6716a83bf4f6