7mqk
AAC(3)-IIIa in complex with CoA and sisomicin
Structural highlights
FunctionAACC3_PSEAI Resistance to antibiotics containing the 2-deoxy-streptamine ring including dibekacin, gentamicin, kanamycin, sisomicin, tobramycin and neomycin, but not to amikacin or netilmicin (PubMed:1649572). Acetylates a broad range of both 4,5- and 4,6-disubstituted aminoglycosides, including neomycin, paromomycin, ribostamycin, sisomicin, gentamicin, tobramycin and kanamycin, with no preference of one disubstitution over the other. Acetylates sisomicin and kanamycin most and least efficiently, respectively. Does not modify plazomicin (PubMed:35921328).[1] [2] Publication Abstract from PubMedCanonical 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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