Short and Sweet: Pac13 is a Small, Monomeric Dehydratase that Mediates the Formation of the 3'- Deoxy Nucleoside of Pacidamycins
The uridyl peptide antibiotics (UPAs), of which pacidamycin is a member, have a clinically unexploited mode of action and an unusual assembly. Perhaps the most striking feature of these molecules is the biosynthetically unique 3'-deoxyuridine that they share. This moiety is generated by an unus...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2017
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| _version_ | 1797081273764675584 |
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| author | Michailidou, F Chung, C Brown, M Bent, A Naismith, J Leavens, W Lynn, S Sharma, S Goss, R |
| author_facet | Michailidou, F Chung, C Brown, M Bent, A Naismith, J Leavens, W Lynn, S Sharma, S Goss, R |
| author_sort | Michailidou, F |
| collection | OXFORD |
| description | The uridyl peptide antibiotics (UPAs), of which pacidamycin is a member, have a clinically unexploited mode of action and an unusual assembly. Perhaps the most striking feature of these molecules is the biosynthetically unique 3'-deoxyuridine that they share. This moiety is generated by an unusual, small and monomeric dehydratase, Pac13, which catalyses the dehydration of uridine-5'-aldehyde. Here we report the structural characterisation of Pac13 with a series of ligands, and gain insight into the enzyme's mechanism demonstrating that H42 is critical to the enzyme's activity and that the reaction is likely to proceed via an E1cB mechanism. The resemblance of the 3'-deoxy pacidamycin moiety with the synthetic anti-retrovirals, presents a potential opportunity for the utilisation of Pac13 in the biocatalytic generation of antiviral compounds. |
| first_indexed | 2024-03-07T01:12:17Z |
| format | Journal article |
| id | oxford-uuid:8d6f86d6-c281-4335-ae6a-58c148b7a1a9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:12:17Z |
| publishDate | 2017 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:8d6f86d6-c281-4335-ae6a-58c148b7a1a92022-03-26T22:51:14ZShort and Sweet: Pac13 is a Small, Monomeric Dehydratase that Mediates the Formation of the 3'- Deoxy Nucleoside of PacidamycinsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8d6f86d6-c281-4335-ae6a-58c148b7a1a9EnglishSymplectic Elements at OxfordWiley2017Michailidou, FChung, CBrown, MBent, ANaismith, JLeavens, WLynn, SSharma, SGoss, RThe uridyl peptide antibiotics (UPAs), of which pacidamycin is a member, have a clinically unexploited mode of action and an unusual assembly. Perhaps the most striking feature of these molecules is the biosynthetically unique 3'-deoxyuridine that they share. This moiety is generated by an unusual, small and monomeric dehydratase, Pac13, which catalyses the dehydration of uridine-5'-aldehyde. Here we report the structural characterisation of Pac13 with a series of ligands, and gain insight into the enzyme's mechanism demonstrating that H42 is critical to the enzyme's activity and that the reaction is likely to proceed via an E1cB mechanism. The resemblance of the 3'-deoxy pacidamycin moiety with the synthetic anti-retrovirals, presents a potential opportunity for the utilisation of Pac13 in the biocatalytic generation of antiviral compounds. |
| spellingShingle | Michailidou, F Chung, C Brown, M Bent, A Naismith, J Leavens, W Lynn, S Sharma, S Goss, R Short and Sweet: Pac13 is a Small, Monomeric Dehydratase that Mediates the Formation of the 3'- Deoxy Nucleoside of Pacidamycins |
| title | Short and Sweet: Pac13 is a Small, Monomeric Dehydratase that Mediates the Formation of the 3'- Deoxy Nucleoside of Pacidamycins |
| title_full | Short and Sweet: Pac13 is a Small, Monomeric Dehydratase that Mediates the Formation of the 3'- Deoxy Nucleoside of Pacidamycins |
| title_fullStr | Short and Sweet: Pac13 is a Small, Monomeric Dehydratase that Mediates the Formation of the 3'- Deoxy Nucleoside of Pacidamycins |
| title_full_unstemmed | Short and Sweet: Pac13 is a Small, Monomeric Dehydratase that Mediates the Formation of the 3'- Deoxy Nucleoside of Pacidamycins |
| title_short | Short and Sweet: Pac13 is a Small, Monomeric Dehydratase that Mediates the Formation of the 3'- Deoxy Nucleoside of Pacidamycins |
| title_sort | short and sweet pac13 is a small monomeric dehydratase that mediates the formation of the 3 deoxy nucleoside of pacidamycins |
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