Structural basis for the inhibition of human lysozyme by PliC from Brucella abortus

Biochemistry. 2013 Dec 23;52(51):9385-93. doi: 10.1021/bi401241c. Epub 2013 Dec 12.


Lysozymes are the first line of defense for a diverse range of organisms that catalyze the degradation of bacterial peptidoglycan. Gram-negative bacteria produce proteinaceous lysozyme inhibitors to protect themselves from the action of lysozymes. To date, MliC or PliC (membrane-bound or periplasmic inhibitor of c-type lysozyme, respectively) has been found in various Gram-negative bacteria. Here, we report the crystal structures of Brucella abortus PliC and its complex with human c-type lysozyme. The complex structure demonstrates that the invariant loop of MliC/PliC plays a crucial role in the inhibition of lysozyme via its insertion into the active site cleft of the lysozyme, as previously observed in the complex structure of Pseudomonas aeruginosa MliC and chicken c-type lysozyme. We identified a new binding interface between a loop adjacent to the active site of human lysozyme and a loop carrying Glu112 of B. abortus PliC, the structure of which was disordered in P. aeruginosa MliC. Because MliC/PliC family members have been implicated as putative colonization or virulence factors, the structures and mechanism of action of MliC/PliC will be relevant to the control of bacterial growth in animal hosts.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Brucella abortus / metabolism*
  • Brucella abortus / pathogenicity
  • Conserved Sequence
  • Crystallography, X-Ray
  • Databases, Protein
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Glutamic Acid / chemistry
  • Humans
  • Models, Molecular*
  • Muramidase / antagonists & inhibitors*
  • Muramidase / chemistry
  • Muramidase / metabolism
  • Mutant Proteins / chemistry
  • Mutant Proteins / metabolism
  • Periplasmic Proteins / chemistry*
  • Periplasmic Proteins / genetics
  • Periplasmic Proteins / metabolism
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Virulence Factors / chemistry*
  • Virulence Factors / genetics
  • Virulence Factors / metabolism


  • Bacterial Proteins
  • Enzyme Inhibitors
  • Escherichia coli Proteins
  • MliC protein, E coli
  • Mutant Proteins
  • Periplasmic Proteins
  • Recombinant Proteins
  • Virulence Factors
  • Glutamic Acid
  • hen egg lysozyme
  • Muramidase
  • lysozyme C, human

Associated data

  • PDB/4MIR
  • PDB/4MIS
  • PDB/4ML7