Molecular basis for substrate recognition and septum cleavage by AtlA, the major N-acetylglucosaminidase of Enterococcus faecalis
| Autor: | Véronique Roig-Zamboni, Sarah Barelier, Robert Dixon, Nicola F. Galley, Amani Ghanem, Quoc Phong Nguyen, Héloize Cahuzac, Bartłomiej Salamaga, Peter J. Davis, Yves Bourne, Stéphane Mesnage, Florence Vincent |
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| Přispěvatelé: | Centre National de la Recherche Scientifique (CNRS), Architecture et fonction des macromolécules biologiques (AFMB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Sheffield [Sheffield], Royal Society (to S. M. and F. V.) (grant no.: IEC∖R2∖170260)., University of Sheffield |
| Rok vydání: | 2022 |
| Předmět: |
structure–function
crystal structure [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Cell Biology Peptidoglycan Biochemistry [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biophysics Bacterial Proteins Acetylglucosaminidase Enterococcus faecalis cell wall Animals glycoside hydrolase [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Molecular Biology ComputingMilieux_MISCELLANEOUS Enterococcus Zebrafish |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, 2022, 298 (5), pp.101915. ⟨10.1016/j.jbc.2022.101915⟩ Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2022, pp.101915. ⟨10.1016/j.jbc.2022.101915⟩ |
| ISSN: | 1083-351X 0021-9258 |
| DOI: | 10.1016/j.jbc.2022.101915⟩ |
| Popis: | International audience; The cleavage of septal peptidoglycan at the end of cell division facilitates the separation of the two daughter cells. The hydrolases involved in this process (called autolysins) are potentially lethal enzymes that can cause cell death; their activity, therefore, must be tightly controlled during cell growth. In Enterococcus faecalis, the N-acetylglucosaminidase AtlA plays a predominant role in cell separation. atlA mutants form long cell chains and are significantly less virulent in the zebrafish model of infection. The attenuated virulence of atlA mutants is underpinned by a limited dissemination of bacterial chains in the host organism and a more efficient uptake by phagocytes that clear the infection. AtlA has structural homologs in other important pathogens, such as Listeria monocytogenes and Salmonella typhimurium, and therefore represents an attractive model to design new inhibitors of bacterial pathogenesis. Here, we provide a 1.45 Å crystal structure of the E. faecalis AtlA catalytic domain that reveals a closed conformation of a conserved β-hairpin and a complex network of hydrogen bonds that bring two catalytic residues to the ideal distance for an inverting mechanism. Based on the model of the AtlA–substrate complex, we identify key residues critical for substrate recognition and septum cleavage during bacterial growth. We propose that this work will provide useful information for the rational design of specific inhibitors targeting this enterococcal virulence factor and its orthologs in other pathogens. |
| Databáze: | OpenAIRE |
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