3RKJ

Crystal Structure of New Delhi Metallo-Beta-Lactamase-1 from Klebsiella pnueumoniae

Summary for 3RKJ

• Entry DOI: 10.2210/pdb3rkj/pdb
• Descriptor: Beta-lactamase NDM-1, SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: structural genomics, psi-biology, midwest center for structural genomics, mcsg, alpha-beta structure, hydrolase, structures of mtb proteins conferring susceptibility to known mtb inhibitors, mtbi
• Biological source: Klebsiella pneumoniae
• Cellular location: Periplasm (Potential): C7C422
• Total number of polymer chains: 2
• Total formula weight: 50218.16

Authors

Kim, Y.,Tesar, C.,Jedrzejczak, R.,Binkowski, T.A.,Babnigg, G.,Sacchettini, J.,Joachimiak, A.,Midwest Center for Structural Genomics (MCSG),Structures of Mtb Proteins Conferring Susceptibility to Known Mtb Inhibitors (MTBI) (deposition date: 2011-04-18, release date: 2011-05-18, Last modification date: 2023-09-13)

Primary citation

Kim, Y.,Tesar, C.,Mire, J.,Jedrzejczak, R.,Binkowski, A.,Babnigg, G.,Sacchettini, J.,Joachimiak, A.
Structure of Apo- and Monometalated Forms of NDM-1 A Highly Potent Carbapenem-Hydrolyzing Metallo-beta-Lactamase
Plos One, 6:e24621-e24621, 2011

PubMed 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.

PubMed: 21931780
DOI: 10.1371/journal.pone.0024621

Experimental method

X-RAY DIFFRACTION (2 Å)