Structure of the LdcB LD-carboxypeptidase reveals the molecular basis of peptidoglycan recognition

Christopher N. Hoyland, Christine Aldridge, Robert M. Cleverley, Marie Clémence Duchêne, George Minasov, Olena Onopriyenko, Karzan Sidiq, Peter J. Stogios, Wayne F. Anderson, Richard A. Daniel, Alexei Savchenko, Waldemar Vollmer, Richard J. Lewis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Peptidoglycan surrounds the bacterial cytoplasmic membrane to protect the cell against osmolysis. The biosynthesis of peptidoglycan, made of glycan strands crosslinked by short peptides, is the target of antibiotics like β-lactams and glycopeptides. Nascent peptidoglycan contains pentapeptides that are trimmed by carboxypeptidases to tetra- and tripeptides. The well-characterized DD-carboxypeptidases hydrolyze the terminal D-alanine from the stem pentapeptide to produce a tetrapeptide. However, few LD-carboxypeptidases that produce tripeptides have been identified, and nothing is known about substrate specificity in these enzymes. We report biochemical properties and crystal structures of the LD-carboxypeptidases LdcB from Streptococcus pneumoniae, Bacillus anthracis, and Bacillus subtilis. The enzymes are active against bacterial cell wall tetrapeptides and adopt a zinc-carboxypeptidase fold characteristic of the LAS superfamily. We have also solved the structure of S. pneumoniae LdcB with a product mimic, elucidating the residues essential for peptidoglycan recognition and the conformational changes that occur on ligand binding.

Original languageEnglish (US)
Pages (from-to)949-960
Number of pages12
JournalStructure
Volume22
Issue number7
DOIs
StatePublished - Jul 8 2014

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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