In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 8 ( 2022-8-3), p. e0269684-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0269684
DOI:
10.1371/journal.pone.0269684.g001
DOI:
10.1371/journal.pone.0269684.g002
DOI:
10.1371/journal.pone.0269684.g003
DOI:
10.1371/journal.pone.0269684.g004
DOI:
10.1371/journal.pone.0269684.g005
DOI:
10.1371/journal.pone.0269684.g006
DOI:
10.1371/journal.pone.0269684.t001
DOI:
10.1371/journal.pone.0269684.t002
DOI:
10.1371/journal.pone.0269684.t003
DOI:
10.1371/journal.pone.0269684.t004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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