Crystal Structures of the SpoIID Lytic Transglycosylases Essential for Bacterial Sporulation

J Biol Chem. 2016 Jul 15;291(29):14915-26. doi: 10.1074/jbc.M116.729749. Epub 2016 May 18.

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.

Keywords: SpoIID; cell differentiation; cell surface enzyme; drug target; enzyme structure; lytic transglycosylase; peptidoglycan; sporulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Bacillus anthracis / enzymology
  • Bacillus anthracis / genetics
  • Bacillus anthracis / pathogenicity
  • Bacillus subtilis / enzymology
  • Bacillus subtilis / genetics
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Catalytic Domain / genetics
  • Clostridium difficile / enzymology
  • Clostridium difficile / genetics
  • Clostridium difficile / pathogenicity
  • Conserved Sequence
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Peptidoglycan Glycosyltransferase / chemistry*
  • Peptidoglycan Glycosyltransferase / genetics
  • Phylogeny
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Spores, Bacterial / enzymology
  • Structural Homology, Protein

Substances

  • Bacterial Proteins
  • spore-specific proteins, Bacillus
  • Peptidoglycan Glycosyltransferase

Associated data

  • PDB/1AM7
  • PDB/1D0K
  • PDB/1D0L
  • PDB/1D0M
  • PDB/1D9U
  • PDB/1E01
  • PDB/1E0G
  • PDB/1LTM
  • PDB/1QDR
  • PDB/1QDT
  • PDB/1QSA
  • PDB/1QTE
  • PDB/1QUS
  • PDB/1QUT
  • PDB/1SLY
  • PDB/2AEO
  • PDB/2G5D
  • PDB/2G6G
  • PDB/2GAE
  • PDB/2PI8
  • PDB/2PIC
  • PDB/2PJJ
  • PDB/2PNW
  • PDB/2Y8P
  • PDB/3BKH
  • PDB/3BKV
  • PDB/3D3D
  • PDB/3T36
  • PDB/4ANR
  • PDB/4C5F
  • PDB/4CFO
  • PDB/4CFP
  • PDB/4CHX
  • PDB/4F55
  • PDB/4FET
  • PDB/4HJV
  • PDB/4HJY
  • PDB/4HJZ
  • PDB/4OWD
  • PDB/4OXV
  • PDB/4OYV
  • PDB/4OZ9
  • PDB/4P0G
  • PDB/4P11
  • PDB/4RWR
  • PDB/5I1T