1MWS

Structure of nitrocefin acyl-Penicillin binding protein 2a from methicillin resistant Staphylococcus aureus strain 27r at 2.00 A resolution.

Summary for 1MWS

• Entry DOI: 10.2210/pdb1mws/pdb
• Related: 1MWR 1MWT 1MWU 1MWX
• Descriptor: penicillin-binding protein 2a, CADMIUM ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: penicillin binding protein, beta-lactam, d, d-transpeptidase, d-carboxypeptidase, nitrocefin, biosynthetic protein
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 149624.58

Authors

Lim, D.C.,Strynadka, N.C.J. (deposition date: 2002-10-01, release date: 2002-11-06, Last modification date: 2011-07-13)

Primary citation

Lim, D.,Strynadka, N.C.
Structural basis for the beta lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus.
Nat.Struct.Biol., 9:870-876, 2002

PubMed Abstract: The multiple antibiotic resistance of methicillin-resistant strains of Staphylococcus aureus (MRSA) has become a major clinical problem worldwide. The key determinant of the broad-spectrum beta-lactam resistance in MRSA strains is the penicillin-binding protein 2a (PBP2a). Because of its low affinity for beta-lactams, PBP2a provides transpeptidase activity to allow cell wall synthesis at beta-lactam concentrations that inhibit the beta-lactam-sensitive PBPs normally produced by S. aureus. The crystal structure of a soluble derivative of PBP2a has been determined to 1.8 A resolution and provides the highest resolution structure for a high molecular mass PBP. Additionally, structures of the acyl-PBP complexes of PBP2a with nitrocefin, penicillin G and methicillin allow, for the first time, a comparison of an apo and acylated resistant PBP. An analysis of the PBP2a active site in these forms reveals the structural basis of its resistance and identifies features in newly developed beta-lactams that are likely important for high affinity binding.

PubMed: 12389036

Experimental method

X-RAY DIFFRACTION (2 Å)