Article Metrics


Online attention

Structure of the LdcB LD-Carboxypeptidase Reveals the Molecular Basis of Peptidoglycan Recognition

DOI: 10.1016/j.str.2014.04.015 DOI Help
PMID: 24909784 PMID Help

Authors: Christopher Hoyland (Newcastle University) , Christine Aldridge (Newcastle University) , Robert Cleverley (Newcastle University) , Marie-clémence Duchêne (Université Catholique de Louvain) , George Minasov (Northwestern University, Chicago) , Olena Onopriyenko (Center for Structural Genomics of Infectious Diseases) , Karzan Sidiq (Newcastle University) , Peter J. Stogios (Center for Structural Genomics of Infectious Diseases) , Wayne F. Anderson (Northwestern University, Chicago) , Richard A. Daniel (Newcastle University) , Alexei Savchenko (Center for Structural Genomics of Infectious Diseases) , Waldemar Vollmer (Newcastle University) , Richard J. Lewis (Newcastle University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure , VOL 22 (7) , PAGES 949 - 960

State: Published (Approved)
Published: July 2014

Open Access Open Access

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.

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography

Discipline Tags:

Technical Tags: