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

ABSTRACT: Bacterial metallo-?-lactamases (MBLs) are involved in resistance to ?-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 ?-lactam and their hydrolysed products are active. This discovery provides a lead for the development of potent and selective SNM1A and SNM1B inhibitors.

SUBMITTER: Lee SY

PROVIDER: S-EPMC5063058 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Lee Sook Y SY Brem Jürgen J Pettinati Ilaria I Claridge Timothy D W TD Gileadi Opher O Schofield Christopher J CJ McHugh Peter J PJ

Chemical communications (Cambridge, England) 20160501 40

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 ar ...[more]

PMID: 27121860

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