1IYQ

Toho-1 beta-Lactamase In Complex With Benzylpenicillin

Summary for 1IYQ

• Entry DOI: 10.2210/pdb1iyq/pdb
• Related: 1IYO 1IYP
• Descriptor: Toho-1 beta-lactamase, SULFATE ION, OPEN FORM - PENICILLIN G, ... (4 entities in total)
• Functional Keywords: beta-lactamase, acyl-enzyme, complex, benzylpenicillin, penicillin g, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 28828.53

Authors

Shimamura, T.,Ibuka, A.,Fushinobu, S.,Wakagi, T.,Ishiguro, M.,Ishii, Y.,Matsuzawa, H. (deposition date: 2002-09-04, release date: 2002-12-11, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.1 Å)