PDBsum entry: 1bue

Hydrolase

PDB id: 1bue

Contents

Protein chain

265 a.a. *

Waters ×115

* Residue conservation analysis

PDB id:

1bue

Name:

Hydrolase

Title:

Nmc-a carbapenemase from enterobacter cloacae

Structure:

Protein (imipenem-hydrolysing beta-lactamase). Chain: a. Synonym: carbapenemase, nmc-a. Engineered: yes

Source:

Enterobacter cloacae. Organism_taxid: 550. Strain: nor-1. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.64Å R-factor: 0.192 R-free: 0.214

Authors:

P.Swaren,L.Maveyraud,S.Cabantous,J.D.Pedelacq,L.Mourey, J.M.Frere,J.P.Samama

Key ref:

P.Swarén et al. (1998). 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. PubMed id: 9756914 DOI: 10.1074/jbc.273.41.26714

Date:

03-Sep-98 Release date: 02-Sep-99

Protein chain

P52663  (BLAN_ENTCL) -  Imipenem-hydrolyzing beta-lactamase

Seq: 292 a.a.

Struc: 265 a.a.

Enzyme reactions

• Enzyme class: E.C.3.5.2.6 - Beta-lactamase.
• Pathway: Penicillin Biosynthesis and Metabolism
• Reaction: A beta-lactam + H₂O = a substituted beta-amino acid
• Cofactor: Zinc

 Gene Ontology (GO) functional annotation 

• Biological process: response to antibiotic (2 terms)
• Biochemical function: hydrolase activity (2 terms)

DOI no: 10.1074/jbc.273.41.26714

J Biol Chem 273:26714-26721 (1998)

PubMed id: 9756914

X-ray analysis of the NMC-A beta-lactamase at 1.64-A resolution, a class A carbapenemase with broad substrate specificity.

P.Swarén, L.Maveyraud, X.Raquet, S.Cabantous, C.Duez, J.D.Pédelacq, S.Mariotte-Boyer, L.Mourey, R.Labia, M.H.Nicolas-Chanoine, P.Nordmann, J.M.Frère, J.P.Samama.

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.

Selected figure(s)

Figure 1.
Fig. 1. Chemical structures of the five classes of -lactam antibiotics. The letters a, b, and c indicate kinetic data from Refs. 16, 42, and 17, respectively. *, not measurable.

Figure 5.
Fig. 5. Stereo view of the hydrogen bond pattern (dotted lines) involving Arg-220 and His-274 in the NMC-A structure. Water molecules are indicated by spheres.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1998, 273, 26714-26721) copyright 1998.

Figures were selected by an automated process.