Identification of Functional Regulatory Residues of the β-Lactam Inducible Penicillin Binding Protein in Methicillin-Resistant Staphylococcus aureus

Abstract EN

Resistance to methicillin by Staphylococcus aureus is a persistent clinical problem worldwide.

A mechanism for resistance has been proposed in which methicillin resistant Staphylococcus aureus (MRSA) isolates acquired a new protein called β-lactam inducible penicillin binding protein (PBP-2′).

The PBP-2′ functions by substituting other penicillin binding proteins which have been inhibited by β-lactam antibiotics.

Presently, there is no structural and regulatory information on PBP-2′ protein.

We conducted a complete structural and functional regulatory analysis of PBP-2′ protein.

Our analysis revealed that the PBP-2′ is very stable with more hydrophilic amino acids expressing antigenic sites.

PBP-2′ has three striking regulatory points constituted by first penicillin binding site at Ser25, second penicillin binding site at Ser405, and finally a single metallic ligand binding site at Glu657 which binds to Zn2+ ions.

This report highlights structural features of PBP-2′ that can serve as targets for developing new chemotherapeutic agents and conducting site direct mutagenesis experiments.