1iyp

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{{STRUCTURE_1iyp| PDB=1iyp | SCENE= }}
{{STRUCTURE_1iyp| PDB=1iyp | SCENE= }}
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'''Toho-1 beta-Lactamase In Complex With Cephalothin'''
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===Toho-1 beta-Lactamase In Complex With Cephalothin===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_12221102}}
==About this Structure==
==About this Structure==
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[[Category: Cephalothin]]
[[Category: Cephalothin]]
[[Category: Complex]]
[[Category: Complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 14:14:09 2008''

Revision as of 11:14, 1 July 2008

Image:1iyp.png

Template:STRUCTURE 1iyp

Toho-1 beta-Lactamase In Complex With Cephalothin

Template:ABSTRACT PUBMED 12221102

About this Structure

1IYP is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

Acyl-intermediate structures of the extended-spectrum class A beta-lactamase, Toho-1, in complex with cefotaxime, cephalothin, and benzylpenicillin., Shimamura T, Ibuka A, Fushinobu S, Wakagi T, Ishiguro M, Ishii Y, Matsuzawa H, J Biol Chem. 2002 Nov 29;277(48):46601-8. Epub 2002 Sep 8. PMID:12221102

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