X-ray Analysis of the NMC-A β-Lactamase at 1.64-Å Resolution, a Class A Carbapenemase with Broad Substrate Specificity

• DOI: 10.1074/jbc.273.41.26714
• Publication Date: 2002-07-26T15:02:22Z
• Authors: Peter Swarén; Laurent Maveyraud; Xavier Raquet; Stéphanie Cabantous; Colette Duez; Jean-Denis Pédelacq; Sophie Mariotte-B...; Lionel Mourey; Roger Labia; Marie-Hélène Nico...; Patrice Nordmann; Jean-Marie Frère; Jean-Pierre Samama
• Keywords: Staphylococcus aureus; 0303 health sciences; Base Sequence; Sequence Homology, Amino Acid; Protein Conformation; [SDV]Life Sciences [q-bio]; Molecular Sequence Data; Bacillus; Crystallography, X-Ray; beta-Lactamases; Substrate Specificity; 3. Good health; Kinetics; 03 medical and health sciences; Amino Acid Sequence; DNA Primers

The treatment of infectious diseases by penicillin and cephalosporin antibiotics is continuously challenged the emergence dissemination numerous TEM SHV mutant β-lactamases with extended substrate profiles. These class A nevertheless remain inefficient against carbapenems, most effective clinically relevant pathogens. new member this enzyme class, NMC-A, was recently reported to hydrolyze at high rates, hence destroy, all known β-lactam antibiotics, including carbapenems cephamycins. crystal structure NMC-A solved 1.64-Å resolution, reveals modifications in topology substrate-binding site. While preserving geometry essential catalytic residues, active site presents a disulfide bridge between residues 69 238, certain other structural differences compared β-lactamases. unusual features involve amino acids that participate enzyme-substrate interactions, which suggested these factors should be related very broad specificity enzyme. comparison those enzymes enzyme-ligand complexes, indicated position Asn-132 provides critical additional space region protein where poorer substrates for β-lactamases, such as cephamycins need accommodated.