Structural highlights
Function
[AACC3_PSEAI] Resistance to antibiotics containing the 2-deoxy-streptamine ring including dibekacin, gentamicin, kanamycin, sisomicin, tobramycin, neomycin and to a lesser extent netilmicin.
Publication Abstract from PubMed
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.
Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa.,Zielinski M, Blanchet J, Hailemariam S, Berghuis AM PLoS One. 2022 Aug 3;17(8):e0269684. doi: 10.1371/journal.pone.0269684., eCollection 2022. PMID:35921328[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zielinski M, Blanchet J, Hailemariam S, Berghuis AM. Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa. PLoS One. 2022 Aug 3;17(8):e0269684. doi: 10.1371/journal.pone.0269684., eCollection 2022. PMID:35921328 doi:http://dx.doi.org/10.1371/journal.pone.0269684
