Structural characterization of MepB from Staphylococcus aureus reveals homology to endonucleases

Protein Sci. 2014 May;23(5):594-602. doi: 10.1002/pro.2438. Epub 2014 Mar 11.

Abstract

The MepRAB operon in Staphylococcus aureus has been identified to play a role in drug resistance. Although the functions of MepA and MepR are known, little information is available on the function of MepB. Here we report the X-ray structure of MepB to 2.1 Å revealing its structural similarity to the PD-(D/E)XK family of endonucleases. We further show that MepB binds DNA and RNA, with a higher affinity towards RNA and single stranded DNA than towards double stranded DNA. Notably, the PD-(D/E)XK catalytic active site residues are not conserved in MepB. MepB's association with a drug resistance operon suggests that it plays a role in responding to antimicrobials. This role is likely carried out through MepB's interactions with nucleic acids.

Keywords: DNA damage; PD-(D/E)XK endonucleases; antimicrobials; drug resistance.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Crystallography, X-Ray
  • DNA / metabolism
  • Drug Resistance, Bacterial
  • Endonucleases / chemistry*
  • Endonucleases / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • RNA / metabolism
  • Sequence Alignment
  • Staphylococcus aureus / chemistry*
  • Staphylococcus aureus / metabolism

Substances

  • Bacterial Proteins
  • RNA
  • DNA
  • Endonucleases

Associated data

  • PDB/1EYU
  • PDB/1F0O
  • PDB/1H56
  • PDB/1K0Z
  • PDB/1NI0
  • PDB/1PVI
  • PDB/1PVU
  • PDB/2OST
  • PDB/2PVI
  • PDB/3DM0
  • PDB/3KSK
  • PDB/3PVI
  • PDB/3RFH
  • PDB/4AOW
  • PDB/4LQE