Crystal structure of the Bacillus subtilis penicillin-binding protein 4a, and its complex with a peptidoglycan mimetic peptide

J Mol Biol. 2007 Aug 10;371(2):528-39. doi: 10.1016/j.jmb.2007.05.071. Epub 2007 Jun 2.

Abstract

The genome of Bacillus subtilis encodes 16 penicillin-binding proteins (PBPs) involved in the synthesis and/or remodelling of the peptidoglycan during the complex life cycle of this sporulating Gram-positive rod-shaped bacterium. PBP4a (encoded by the dacC gene) is a low-molecular mass PBP clearly exhibiting in vitro DD-carboxypeptidase activity. We have solved the crystal structure of this protein alone and in complex with a peptide (D-alpha-aminopymelyl-epsilon-D-alanyl-D-alanine) that mimics the C-terminal end of the Bacillus peptidoglycan stem peptide. PBP4a is composed of three domains: the penicillin-binding domain with a fold similar to the class A beta-lactamase structure and two domains inserted between the conserved motifs 1 and 2 characteristic of the penicillin-recognizing enzymes. The soaking of PBP4a in a solution of D-alpha-aminopymelyl-epsilon-D-alanyl-D-alanine resulted in an adduct between PBP4a and a D-alpha-aminopimelyl-epsilon-D-alanine dipeptide and an unbound D-alanine, i.e. the products of acylation of PBP4a by D-alpha-aminopymelyl-epsilon-D-alanyl-D-alanine with the release of a D-alanine. The adduct also reveals a binding pocket specific to the diaminopimelic acid, the third residue of the peptidoglycan stem pentapeptide of B. subtilis. This pocket is specific for this class of PBPs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacillus subtilis / chemistry*
  • Bacillus subtilis / genetics
  • Bacillus subtilis / metabolism*
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / metabolism*
  • Crystallography, X-Ray
  • Lactams / chemistry
  • Lactams / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Penicillin-Binding Proteins / chemistry*
  • Penicillin-Binding Proteins / genetics
  • Penicillin-Binding Proteins / metabolism*
  • Peptides / chemistry
  • Peptides / metabolism*
  • Peptidoglycan / chemistry
  • Peptidoglycan / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Sensitivity and Specificity
  • Sequence Alignment

Substances

  • Lactams
  • Penicillin-Binding Proteins
  • Peptides
  • Peptidoglycan

Associated data

  • PDB/1W5D
  • PDB/2J9P