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Structure of Apo- and Monometalated Forms of NDM-1-A Highly Potent Carbapenem-Hydrolyzing Metallo-beta-Lactamase | Academic Article individual record
abstract

The New Delhi Metallo-β-lactamase (NDM-1) gene makes multiple pathogenic microorganisms resistant to all known β-lactam antibiotics. The rapid emergence of NDM-1 has been linked to mobile plasmids that move between different strains resulting in world-wide dissemination. Biochemical studies revealed that NDM-1 is capable of efficiently hydrolyzing a wide range of β-lactams, including many carbapenems considered as \"last resort\" antibiotics. The crystal structures of metal-free apo- and monozinc forms of NDM-1 presented here revealed an enlarged and flexible active site of class B1 metallo-β-lactamase. This site is capable of accommodating many β-lactam substrates by having many of the catalytic residues on flexible loops, which explains the observed extended spectrum activity of this zinc dependent β-lactamase. Indeed, five loops contribute \"keg\" residues in the active site including side chains involved in metal binding. Loop 1 in particular, shows conformational flexibility, apparently related to the acceptance and positioning of substrates for cleavage by a zinc-activated water molecule.

author list (cited authors)
Kim, Y., Tesar, C., Mire, J., Jedrzejczak, R., Binkowski, A., Babnigg, G., Sacchettini, J., & Joachimiak, A.
publication date
2011
published in
PLoS ONE Journal
keywords
  • Carbapenems
  • Enterobacteriaceae
  • Beta-Lactamases
  • Chromatography, Gel
  • Protein Structure, Secondary
  • X-Ray Diffraction
altmetric score

8.056

citation count

58