4EY2

Crystal structure of NDM-1 bound to hydrolyzed methicillin

4EY2 の概要

• エントリーDOI: 10.2210/pdb4ey2/pdb
• 関連するPDBエントリー: 3Q6X 3SPU 4EXS 4EXY 4EYB 4EYF 4EYL
• 分子名称: Beta-lactamase NDM-1, (2R,4S)-2-{(R)-carboxy[(2,6-dimethoxybenzoyl)amino]methyl}-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid, ZINC ION, ... (4 entities in total)
• 機能のキーワード: metallo-beta-lactamase, antibiotic, hydrolase-antibiotic complex, hydrolase/antibiotic
• 由来する生物種: Klebsiella pneumoniae
• 細胞内の位置: Periplasm : C7C422
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58178.76

構造登録者

Strynadka, N.C.J.,King, D.T. (登録日: 2012-05-01, 公開日: 2012-08-08, 最終更新日: 2024-02-28)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.17 Å)