Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa.
Canonical aminoglycosides are a large group of antibiotics, where the part of chemical diversity stems from the substitution of the neamine ring system on positions 5 and 6. Certain aminoglycoside modifying enzymes can modify a broad range of 4,5- and 4,6-disubstituted aminoglycosides, with some as...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0269684 |
| _version_ | 1811283298639413248 |
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| author | Michał Zieliński Jonathan Blanchet Sophia Hailemariam Albert M Berghuis |
| author_facet | Michał Zieliński Jonathan Blanchet Sophia Hailemariam Albert M Berghuis |
| author_sort | Michał Zieliński |
| collection | DOAJ |
| description | Canonical aminoglycosides are a large group of antibiotics, where the part of chemical diversity stems from the substitution of the neamine ring system on positions 5 and 6. Certain aminoglycoside modifying enzymes can modify a broad range of 4,5- and 4,6-disubstituted aminoglycosides, with some as many as 15. This study presents the structural and kinetic results describing a promiscuous aminoglycoside acetyltransferase AAC(3)-IIIa. This enzyme has been crystallized in ternary complex with coenzyme A and 4,5- and 4,6-disubstituted aminoglycosides. We have followed up this work with kinetic characterization utilizing a panel of diverse aminoglycosides, including a next-generation aminoglycoside, plazomicin. Lastly, we observed an alternative binding mode of gentamicin in the aminoglycoside binding site, which was proven to be a crystallographic artifact based on mutagenesis. |
| first_indexed | 2024-04-13T02:08:57Z |
| format | Article |
| id | doaj.art-120e16bcfab34acd994c69bef0d1f75e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T02:08:57Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-120e16bcfab34acd994c69bef0d1f75e2022-12-22T03:07:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01178e026968410.1371/journal.pone.0269684Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa.Michał ZielińskiJonathan BlanchetSophia HailemariamAlbert M BerghuisCanonical aminoglycosides are a large group of antibiotics, where the part of chemical diversity stems from the substitution of the neamine ring system on positions 5 and 6. Certain aminoglycoside modifying enzymes can modify a broad range of 4,5- and 4,6-disubstituted aminoglycosides, with some as many as 15. This study presents the structural and kinetic results describing a promiscuous aminoglycoside acetyltransferase AAC(3)-IIIa. This enzyme has been crystallized in ternary complex with coenzyme A and 4,5- and 4,6-disubstituted aminoglycosides. We have followed up this work with kinetic characterization utilizing a panel of diverse aminoglycosides, including a next-generation aminoglycoside, plazomicin. Lastly, we observed an alternative binding mode of gentamicin in the aminoglycoside binding site, which was proven to be a crystallographic artifact based on mutagenesis.https://doi.org/10.1371/journal.pone.0269684 |
| spellingShingle | Michał Zieliński Jonathan Blanchet Sophia Hailemariam Albert M Berghuis Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa. PLoS ONE |
| title | Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa. |
| title_full | Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa. |
| title_fullStr | Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa. |
| title_full_unstemmed | Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa. |
| title_short | Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa. |
| title_sort | structural elucidation of substrate bound aminoglycoside acetyltransferase 3 iiia |
| url | https://doi.org/10.1371/journal.pone.0269684 |
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