Binding of (5S)-penicilloic acid to penicillin binding protein 3.
β-Lactam antibiotics react with penicillin binding proteins (PBPs) to form relatively stable acyl-enzyme complexes. We describe structures derived from the reaction of piperacillin with PBP3 (Pseudomonas aeruginosa) including not only the anticipated acyl-enzyme complex but also an unprecedented com...
Hauptverfasser: | , , , , , , , , , , |
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Format: | Journal article |
Sprache: | English |
Veröffentlicht: |
2013
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_version_ | 1826272447702237184 |
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author | van Berkel, S Nettleship, J Leung, I Brem, J Choi, H Stuart, D Claridge, T McDonough, M Owens, R Ren, J Schofield, C |
author_facet | van Berkel, S Nettleship, J Leung, I Brem, J Choi, H Stuart, D Claridge, T McDonough, M Owens, R Ren, J Schofield, C |
author_sort | van Berkel, S |
collection | OXFORD |
description | β-Lactam antibiotics react with penicillin binding proteins (PBPs) to form relatively stable acyl-enzyme complexes. We describe structures derived from the reaction of piperacillin with PBP3 (Pseudomonas aeruginosa) including not only the anticipated acyl-enzyme complex but also an unprecedented complex with (5S)-penicilloic acid, which was formed by C-5 epimerization of the nascent (5R)-penicilloic acid product. Formation of the complex was confirmed by solution studies, including NMR. Together, these results will be useful in the design of new PBP inhibitors and raise the possibility that noncovalent PBP inhibition by penicilloic acids may be of clinical relevance. |
first_indexed | 2024-03-06T22:12:43Z |
format | Journal article |
id | oxford-uuid:525ab63b-c6e6-408f-b1bb-b842e948d8cb |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-06T22:12:43Z |
publishDate | 2013 |
record_format | dspace |
spelling | oxford-uuid:525ab63b-c6e6-408f-b1bb-b842e948d8cb2022-03-26T16:25:08ZBinding of (5S)-penicilloic acid to penicillin binding protein 3.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:525ab63b-c6e6-408f-b1bb-b842e948d8cbEnglishSymplectic Elements at Oxford2013van Berkel, SNettleship, JLeung, IBrem, JChoi, HStuart, DClaridge, TMcDonough, MOwens, RRen, JSchofield, Cβ-Lactam antibiotics react with penicillin binding proteins (PBPs) to form relatively stable acyl-enzyme complexes. We describe structures derived from the reaction of piperacillin with PBP3 (Pseudomonas aeruginosa) including not only the anticipated acyl-enzyme complex but also an unprecedented complex with (5S)-penicilloic acid, which was formed by C-5 epimerization of the nascent (5R)-penicilloic acid product. Formation of the complex was confirmed by solution studies, including NMR. Together, these results will be useful in the design of new PBP inhibitors and raise the possibility that noncovalent PBP inhibition by penicilloic acids may be of clinical relevance. |
spellingShingle | van Berkel, S Nettleship, J Leung, I Brem, J Choi, H Stuart, D Claridge, T McDonough, M Owens, R Ren, J Schofield, C Binding of (5S)-penicilloic acid to penicillin binding protein 3. |
title | Binding of (5S)-penicilloic acid to penicillin binding protein 3. |
title_full | Binding of (5S)-penicilloic acid to penicillin binding protein 3. |
title_fullStr | Binding of (5S)-penicilloic acid to penicillin binding protein 3. |
title_full_unstemmed | Binding of (5S)-penicilloic acid to penicillin binding protein 3. |
title_short | Binding of (5S)-penicilloic acid to penicillin binding protein 3. |
title_sort | binding of 5s penicilloic acid to penicillin binding protein 3 |
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