Crystallographic analysis of Staphylococcus aureus LcpA, the primary wall teichoic acid ligase
| Autor: | Federico I. Rosell, Jean-Pierre Simorre, Natalie C. J. Strynadka, Eric D. Brown, Robert T. Gale, Franco K.K. Li |
|---|---|
| Přispěvatelé: | Centre for Blood Research (CBR), University of British Columbia (UBC), Department of Biochemistry and Biomedical Sciences, McMaster University [Hamilton, Ontario], Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
size-exclusion chromatography with multiangle light scattering MESH: Molecular Structure MESH: Catalytic Domain Bacillus Bacillus subtilis peptidoglycan Biochemistry Bacterial cell structure oligomerization Cell wall 03 medical and health sciences chemistry.chemical_compound MESH: Cell Wall Arabinogalactan MESH: Staphylococcus aureus MESH: Protein Binding Molecular Biology MESH: Bacterial Proteins X-ray crystallography chemistry.chemical_classification Teichoic acid DNA ligase 030102 biochemistry & molecular biology biology [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] MESH: Peptidoglycan Cell Biology MESH: Bacillus subtilis biology.organism_classification MESH: Crystallography X-Ray teichoic acid LytR–CpsA–Psr Staphylococcus aureus (S. aureus) 030104 developmental biology Enzyme chemistry MESH: Ligases gram-positive bacteria MESH: Teichoic Acids cell wall Peptidoglycan |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, 2020, 295 (9), pp.2629-2639. ⟨10.1074/jbc.RA119.011469⟩ Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2020, 295 (9), pp.2629-2639. ⟨10.1074/jbc.RA119.011469⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.RA119.011469⟩ |
| Popis: | International audience; Gram-positive bacteria, including major clinical pathogens such as Staphylococcus aureus, are becoming increasingly drug-resistant. Their cell walls are composed of a thick layer of peptidoglycan (PG) modified by the attachment of wall teichoic acid (WTA), an anionic glycopolymer that is linked to pathogenicity and regulation of cell division and PG synthesis. The transfer of WTA from lipid carriers to PG, catalyzed by the LytR-CpsA-Psr (LCP) enzyme family, offers a unique extracellular target for the development of new anti-infective agents. Inhibitors of LCP enzymes have the potential to manage a wide range of bacterial infections because the target enzymes are implicated in the assembly of many other bacterial cell wall polymers, including capsular polysaccharide of streptococcal species and arabinogalactan of mycobacterial species. In this study, we present the first crystal structure of S. aureus LcpA with bound substrate at 1.9 Å resolution and those of Bacillus subtilis LCP enzymes, TagT, TagU, and TagV, in the apo form at 1.6-2.8 Å resolution. The structures of these WTA transferases provide new insight into the binding of lipid-linked WTA and enable assignment of the catalytic roles of conserved active-site residues. Furthermore, we identified potential subsites for binding the saccharide core of PG using computational docking experiments, and multiangle light-scattering experiments disclosed novel oligomeric states of the LCP enzymes. The crystal structures and modeled substrate-bound complexes of the LCP enzymes reported here provide insights into key features linked to substrate binding and catalysis and may aid the structure-guided design of specific LCP inhibitors. |
| Databáze: | OpenAIRE |
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