4EYB

Crystal structure of NDM-1 bound to hydrolyzed oxacillin

Summary for 4EYB

• Entry DOI: 10.2210/pdb4eyb/pdb
• Related: 3Q6X 3SPU 4EXS 4EXY 4EY2 4EYF 4EYL
• Descriptor: Beta-lactamase NDM-1, ZINC ION, (2R,4S)-2-[(R)-carboxy{[(5-methyl-3-phenyl-1,2-oxazol-4-yl)carbonyl]amino}methyl]-5,5-dimethyl-1,3-thiazolidine-4-carbo xylic acid, ... (4 entities in total)
• Functional Keywords: metallo beta lactamase, antibiotic, hydrolase-antibiotic complex, hydrolase/antibiotic
• Biological source: Klebsiella pneumoniae
• Cellular location: Periplasm : C7C422
• Total number of polymer chains: 2
• Total formula weight: 58220.81

Authors

Strynadka, N.C.J.,King, D.T. (deposition date: 2012-05-01, release date: 2012-08-15, Last modification date: 2024-02-28)

Primary citation

King, D.T.,Worrall, L.J.,Gruninger, R.,Strynadka, N.C.
New Delhi Metallo-Beta-Lactamase: Structural Insights into Beta-Lactam Recognition and Inhibition
J.Am.Chem.Soc., 134:11362-11365, 2012

PubMed Abstract: The β-lactam antibiotics have long been a cornerstone for the treatment of bacterial disease. Recently, a readily transferable antibiotic resistance factor called the New Delhi metallo-β-lactamase-1 (NDM-1) has been found to confer enteric bacteria resistance to nearly all β-lactams, including the heralded carbapenems, posing a serious threat to human health. The crystal structure of NDM-1 bound to meropenem shows for the first time the molecular details of how carbapenem antibiotics are recognized by dizinc-containing metallo-β-lactamases. Additionally, product complex structures of hydrolyzed benzylpenicillin-, methicillin-, and oxacillin-bound NDM-1 have been solved to 1.8, 1.2, and 1.2 Å, respectively, and represent the highest-resolution structural data for any metallo-β-lactamase reported to date. Finally, we present the crystal structure of NDM-1 bound to the potent competitive inhibitor l-captopril, which reveals a unique binding mechanism. An analysis of the NDM-1 active site in these structures reveals key features important for the informed design of novel inhibitors of NDM-1 and other metallo-β-lactamases.

PubMed: 22713171
DOI: 10.1021/ja303579d

Experimental method

X-RAY DIFFRACTION (1.16 Å)