Ribosome protection by ABC‐F proteins — molecular mechanism and potential drug design
Members of the ATP‐binding cassette F (ABC‐F) proteins confer resistance to several classes of clinically important antibiotics through ribosome protection. Recent structures of two ABC‐F proteins, Pseudomonas aeruginosa MsrE and Bacillus subtilis VmlR bound to ribosome have shed light onto the ribo...
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| Format: | Journal Article |
| Language: | English |
| Published: |
2019
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| Online Access: | https://hdl.handle.net/10356/104616 http://hdl.handle.net/10220/49511 |
| _version_ | 1826109984574799872 |
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| author | Ero, Rya Kumar, Veerendra Su, Weixin Gao, Yong‐Gui |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Ero, Rya Kumar, Veerendra Su, Weixin Gao, Yong‐Gui |
| author_sort | Ero, Rya |
| collection | NTU |
| description | Members of the ATP‐binding cassette F (ABC‐F) proteins confer resistance to several classes of clinically important antibiotics through ribosome protection. Recent structures of two ABC‐F proteins, Pseudomonas aeruginosa MsrE and Bacillus subtilis VmlR bound to ribosome have shed light onto the ribosome protection mechanism whereby drug resistance is mediated by the antibiotic resistance domain (ARD) connecting the two ATP binding domains. ARD of the E site bound MsrE and VmlR extends toward the drug binding region within the peptidyl transferase center (PTC) and leads to conformational changes in the P site tRNA acceptor stem, the PTC, and the drug binding site causing the release of corresponding drugs. The structural similarities and differences of the MsrE and VmlR structures likely highlight an universal ribosome protection mechanism employed by antibiotic resistance (ARE) ABC‐F proteins. The variable ARD domains enable this family of proteins to adapt the protection mechanism for several classes of ribosome‐targeting drugs. ARE ABC‐F genes have been found in numerous pathogen genomes and multi‐drug resistance conferring plasmids. Collectively they mediate resistance to a broader range of antimicrobial agents than any other group of resistance proteins and play a major role in clinically significant drug resistance in pathogenic bacteria. Here, we review the recent structural and biochemical findings on these emerging resistance proteins, offering an update of the molecular basis and implications for overcoming ABC‐F conferred drug resistance. |
| first_indexed | 2024-10-01T02:27:22Z |
| format | Journal Article |
| id | ntu-10356/104616 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:27:22Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/1046162020-03-07T12:18:17Z Ribosome protection by ABC‐F proteins — molecular mechanism and potential drug design Ero, Rya Kumar, Veerendra Su, Weixin Gao, Yong‐Gui School of Biological Sciences NTU Institute of Structural Biology Antibiotic Resistance Ribosome Protection Science::Biological sciences Members of the ATP‐binding cassette F (ABC‐F) proteins confer resistance to several classes of clinically important antibiotics through ribosome protection. Recent structures of two ABC‐F proteins, Pseudomonas aeruginosa MsrE and Bacillus subtilis VmlR bound to ribosome have shed light onto the ribosome protection mechanism whereby drug resistance is mediated by the antibiotic resistance domain (ARD) connecting the two ATP binding domains. ARD of the E site bound MsrE and VmlR extends toward the drug binding region within the peptidyl transferase center (PTC) and leads to conformational changes in the P site tRNA acceptor stem, the PTC, and the drug binding site causing the release of corresponding drugs. The structural similarities and differences of the MsrE and VmlR structures likely highlight an universal ribosome protection mechanism employed by antibiotic resistance (ARE) ABC‐F proteins. The variable ARD domains enable this family of proteins to adapt the protection mechanism for several classes of ribosome‐targeting drugs. ARE ABC‐F genes have been found in numerous pathogen genomes and multi‐drug resistance conferring plasmids. Collectively they mediate resistance to a broader range of antimicrobial agents than any other group of resistance proteins and play a major role in clinically significant drug resistance in pathogenic bacteria. Here, we review the recent structural and biochemical findings on these emerging resistance proteins, offering an update of the molecular basis and implications for overcoming ABC‐F conferred drug resistance. 2019-08-01T05:54:42Z 2019-12-06T21:36:19Z 2019-08-01T05:54:42Z 2019-12-06T21:36:19Z 2019 Journal Article Ero, R., Kumar, V., Su, W., & Gao, Y.-G. (2019). Ribosome protection by ABC‐F proteins — molecular mechanism and potential drug design. Protein Science, 28(4), 684-693. doi:10.1002/pro.3589 0961-8368 https://hdl.handle.net/10356/104616 http://hdl.handle.net/10220/49511 10.1002/pro.3589 en Protein Science © 2019 The Protein Society. All rights reserved. |
| spellingShingle | Antibiotic Resistance Ribosome Protection Science::Biological sciences Ero, Rya Kumar, Veerendra Su, Weixin Gao, Yong‐Gui Ribosome protection by ABC‐F proteins — molecular mechanism and potential drug design |
| title | Ribosome protection by ABC‐F proteins — molecular mechanism and potential drug design |
| title_full | Ribosome protection by ABC‐F proteins — molecular mechanism and potential drug design |
| title_fullStr | Ribosome protection by ABC‐F proteins — molecular mechanism and potential drug design |
| title_full_unstemmed | Ribosome protection by ABC‐F proteins — molecular mechanism and potential drug design |
| title_short | Ribosome protection by ABC‐F proteins — molecular mechanism and potential drug design |
| title_sort | ribosome protection by abc f proteins molecular mechanism and potential drug design |
| topic | Antibiotic Resistance Ribosome Protection Science::Biological sciences |
| url | https://hdl.handle.net/10356/104616 http://hdl.handle.net/10220/49511 |
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