1BUE

NMC-A CARBAPENEMASE FROM ENTEROBACTER CLOACAE

Summary for 1BUE

• Entry DOI: 10.2210/pdb1bue/pdb
• Descriptor: PROTEIN (IMIPENEM-HYDROLYSING BETA-LACTAMASE) (2 entities in total)
• Functional Keywords: hydrolase, antibiotic resistance, class a carbapenemase
• Biological source: Enterobacter cloacae
• Total number of polymer chains: 1
• Total formula weight: 29137.60

Authors

Swaren, P.,Maveyraud, L.,Cabantous, S.,Pedelacq, J.D.,Mourey, L.,Frere, J.M.,Samama, J.P. (deposition date: 1998-09-03, release date: 1999-09-02, Last modification date: 2024-10-30)

Primary citation

Swaren, P.,Maveyraud, L.,Raquet, X.,Cabantous, S.,Duez, C.,Pedelacq, J.D.,Mariotte-Boyer, S.,Mourey, L.,Labia, R.,Nicolas-Chanoine, M.H.,Nordmann, P.,Frere, J.M.,Samama, J.P.
X-ray analysis of the NMC-A beta-lactamase at 1.64-A resolution, a class A carbapenemase with broad substrate specificity.
J.Biol.Chem., 273:26714-26721, 1998

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

PubMed: 9756914
DOI: 10.1074/jbc.273.41.26714

Experimental method

X-RAY DIFFRACTION (1.64 Å)