1IYO

Toho-1 beta-Lactamase In Complex With Cefotaxime

1IYO の概要

• エントリーDOI: 10.2210/pdb1iyo/pdb
• 関連するPDBエントリー: 1IYP 1IYQ
• 分子名称: Toho-1 beta-lactamase, SULFATE ION, CEFOTAXIME, C3' cleaved, open, bound form, ... (4 entities in total)
• 機能のキーワード: extended-spectrum, esbl, beta-lactamase, acyl-enzyme, cefotaxime, complex, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28889.55

構造登録者

Shimamura, T.,Ibuka, A.,Fushinobu, S.,Wakagi, T.,Ishiguro, M.,Ishii, Y.,Matsuzawa, H. (登録日: 2002-09-04, 公開日: 2002-12-11, 最終更新日: 2024-11-20)

主引用文献

Shimamura, T.,Ibuka, A.,Fushinobu, S.,Wakagi, T.,Ishiguro, M.,Ishii, Y.,Matsuzawa, H.
Acyl-intermediate Structures of the Extended-spectrum Class A beta -Lactamase, Toho-1, in Complex with Cefotaxime, Cephalothin, and Benzylpenicillin.
J.Biol.Chem., 277:46601-46608, 2002

PubMed Abstract: Bacterial resistance to beta-lactam antibiotics is a serious problem limiting current clinical therapy. The most common form of resistance is the production of beta-lactamases that inactivate beta-lactam antibiotics. Toho-1 is an extended-spectrum beta-lactamase that has acquired efficient activity not only to penicillins but also to cephalosporins including the expanded-spectrum cephalosporins that were developed to be stable in former beta-lactamases. We present the acyl-intermediate structures of Toho-1 in complex with cefotaxime (expanded-spectrum cephalosporin), cephalothin (non-expanded-spectrum cephalosporin), and benzylpenicillin at 1.8-, 2.0-, and 2.1-A resolutions, respectively. These structures reveal distinct features that can explain the ability of Toho-1 to hydrolyze expanded-spectrum cephalosporins. First, the Omega-loop of Toho-1 is displaced to avoid the steric contacts with the bulky side chain of cefotaxime. Second, the conserved residues Asn(104) and Asp(240) form unique interactions with the bulky side chain of cefotaxime to fix it tightly. Finally, the unique interaction between the conserved Ser(237) and cephalosporins probably helps to bring the beta-lactam carbonyl group to the suitable position in the oxyanion hole, thus increasing the cephalosporinase activity.

PubMed: 12221102
DOI: 10.1074/jbc.M207884200

実験手法

X-RAY DIFFRACTION (1.8 Å)