Cephalosporins inhibit human metallo β-lactamase fold DNA repair nucleases SNM1A and SNM1B/apollo

Cephalosporins inhibit human metallo β-lactamase fold DNA repair nucleases SNM1A and SNM1B/apollo

Bacterial metallo-β-lactamases (MBLs) are involved in resistance to β-lactam antibiotics including cephalosporins. Human SNM1A and SNM1B are MBL superfamily exonucleases that play a key role in the repair of DNA interstrand cross-links, which are induced by antitumour chemotherapeutics, and are ther...

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Bibliographic Details
Main Authors: Lee, S, Brem, J, Pettinati, I, Claridge, T, Gileadi, O, Schofield, C, McHugh, P
Format: Journal article
Published: Royal Society of Chemistry 2016
Description
Summary:Bacterial metallo-β-lactamases (MBLs) are involved in resistance to β-lactam antibiotics including cephalosporins. Human SNM1A and SNM1B are MBL superfamily exonucleases that play a key role in the repair of DNA interstrand cross-links, which are induced by antitumour chemotherapeutics, and are therefore targets for cancer chemosensitization. We report that cephalosporins are competitive inhibitors of SNM1A and SNM1B exonuclease activity; both the intact β-lactam and their hydrolysed products are active. This discovery provides a lead for the development of potent and selective SNM1A and SNM1B inhibitors.

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