Penicillin binding protein 2a: An overview and a medicinal chemistry perspective

Eur J Med Chem. 2020 Aug 1:199:112312. doi: 10.1016/j.ejmech.2020.112312. Epub 2020 Apr 18.


Antimicrobial resistance is an imminent threat worldwide. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the "superbug" family, manifesting resistance through the production of a penicillin binding protein, PBP2a, an enzyme that provides its transpeptidase activity to allow cell wall biosynthesis. PBP2a's low affinity to most β-lactams, confers resistance to MRSA against numerous members of this class of antibiotics. An Achilles' heel of MRSA, PBP2a represents a substantial target to design novel antibiotics to tackle MRSA threat via inhibition of the bacterial cell wall biosynthesis. In this review we bring into focus the PBP2a enzyme and examine the various aspects related to its role in conferring resistance to MRSA strains. Moreover, we discuss several antibiotics and antimicrobial agents designed to target PBP2a and their therapeutic potential to meet such a grave threat. In conclusion, we consider future perspectives for targeting MRSA infections.

Keywords: Allosteric control; Anti-MRSA; Antimicrobial resistance; Enzyme inhibitor; Penicillin binding protein 2a; β-lactams.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Chemistry, Pharmaceutical
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / enzymology
  • Microbial Sensitivity Tests
  • Penicillin-Binding Proteins / antagonists & inhibitors*
  • Penicillin-Binding Proteins / metabolism


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Enzyme Inhibitors
  • Penicillin-Binding Proteins
  • mecA protein, Staphylococcus aureus