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...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
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Royal Society of Chemistry
2016
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| _version_ | 1797075585708589056 |
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| author | Lee, S Brem, J Pettinati, I Claridge, T Gileadi, O Schofield, C McHugh, P |
| author_facet | Lee, S Brem, J Pettinati, I Claridge, T Gileadi, O Schofield, C McHugh, P |
| author_sort | Lee, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T23:52:24Z |
| format | Journal article |
| id | oxford-uuid:730cdf6e-f3e1-41c4-8022-bfc600cbadf4 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T23:52:24Z |
| publishDate | 2016 |
| publisher | Royal Society of Chemistry |
| record_format | dspace |
| spelling | oxford-uuid:730cdf6e-f3e1-41c4-8022-bfc600cbadf42022-03-26T19:54:01ZCephalosporins inhibit human metallo β-lactamase fold DNA repair nucleases SNM1A and SNM1B/apolloJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:730cdf6e-f3e1-41c4-8022-bfc600cbadf4Symplectic Elements at OxfordRoyal Society of Chemistry2016Lee, SBrem, JPettinati, IClaridge, TGileadi, OSchofield, CMcHugh, PBacterial 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. |
| spellingShingle | Lee, S Brem, J Pettinati, I Claridge, T Gileadi, O Schofield, C McHugh, P Cephalosporins inhibit human metallo β-lactamase fold DNA repair nucleases SNM1A and SNM1B/apollo |
| title | Cephalosporins inhibit human metallo β-lactamase fold DNA repair nucleases SNM1A and SNM1B/apollo |
| title_full | Cephalosporins inhibit human metallo β-lactamase fold DNA repair nucleases SNM1A and SNM1B/apollo |
| title_fullStr | Cephalosporins inhibit human metallo β-lactamase fold DNA repair nucleases SNM1A and SNM1B/apollo |
| title_full_unstemmed | Cephalosporins inhibit human metallo β-lactamase fold DNA repair nucleases SNM1A and SNM1B/apollo |
| title_short | Cephalosporins inhibit human metallo β-lactamase fold DNA repair nucleases SNM1A and SNM1B/apollo |
| title_sort | cephalosporins inhibit human metallo β lactamase fold dna repair nucleases snm1a and snm1b apollo |
| work_keys_str_mv | AT lees cephalosporinsinhibithumanmetalloblactamasefolddnarepairnucleasessnm1aandsnm1bapollo AT bremj cephalosporinsinhibithumanmetalloblactamasefolddnarepairnucleasessnm1aandsnm1bapollo AT pettinatii cephalosporinsinhibithumanmetalloblactamasefolddnarepairnucleasessnm1aandsnm1bapollo AT claridget cephalosporinsinhibithumanmetalloblactamasefolddnarepairnucleasessnm1aandsnm1bapollo AT gileadio cephalosporinsinhibithumanmetalloblactamasefolddnarepairnucleasessnm1aandsnm1bapollo AT schofieldc cephalosporinsinhibithumanmetalloblactamasefolddnarepairnucleasessnm1aandsnm1bapollo AT mchughp cephalosporinsinhibithumanmetalloblactamasefolddnarepairnucleasessnm1aandsnm1bapollo |