Crystal structures of the spoiid lytic transglycosylases essential for bacterial sporulation

Salvatore Nocadello, George Minasov, Ludmilla S. Shuvalova, Ievgeniia Dubrovska, Elisabetta Sabini, Wayne F. Anderson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Bacterial spores are the most resistant form of life known on Earth and represent a serious problem for (i) bioterrorism attack, (ii) horizontal transmission of microbial pathogens in the community, and (iii) persistence in patients and in a nosocomial environment. Stage II sporulation protein D (SpoIID) is a lytic transglycosylase (LT) essential for sporulation. The LT superfamily is a potential drug target because it is active in essential bacterial processes involving the peptidoglycan, which is unique to bacteria. However, the absence of structural information for the sporulation-specific LT enzymes has hindered mechanistic understanding of SpoIID. Here, we report the first crystal structures with and without ligands of the SpoIID family from two community relevant spore-forming pathogens, Bacillus anthracis and Clostridium difficile. The structures allow us to visualize the overall architecture, characterize the substrate recognition model, identify critical residues, and provide the structural basis for catalysis by this new family of enzymes.

Original languageEnglish (US)
Pages (from-to)14915-14926
Number of pages12
JournalJournal of Biological Chemistry
Volume291
Issue number29
DOIs
StatePublished - Jul 15 2016

Funding

This work was supported by National Institutes of Health Contracts HHSN272200700058C and HHSN272201200026C from NIAID (to Structural Genomics of Infectious Diseases). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. X-ray data collection was done at the LS-CAT beamlines 21ID-G (3ROH) and 21ID-F (4Q7G) at the Advanced Photon Source Science User Facility operated for the United States Department of Energy (DOE), supported by the United States Department of Energy under Contract Number DE-AC02-06CH11357.

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Cell Biology

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