7MQK

AAC(3)-IIIa in complex with CoA and sisomicin

Summary for 7MQK

• Entry DOI: 10.2210/pdb7mqk/pdb
• Descriptor: Aminoglycoside N(3)-acetyltransferase III, (1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy}-2-hydroxycyclohexyl 3-deoxy-4-C-methyl-3-(methylamino)-beta-L-arabinopyranoside, COENZYME A, ... (5 entities in total)
• Functional Keywords: antibiotic resistance, aminoglycoside, acetyltransferase, transferase
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 4
• Total formula weight: 124744.11

Authors

Zielinski, M.,Berghuis, A.M. (deposition date: 2021-05-05, release date: 2022-07-06, Last modification date: 2024-10-23)

Primary citation

Zielinski, M.,Blanchet, J.,Hailemariam, S.,Berghuis, A.M.
Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa.
Plos One, 17:e0269684-e0269684, 2022

PubMed 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.

PubMed: 35921328
DOI: 10.1371/journal.pone.0269684

Experimental method

X-RAY DIFFRACTION (1.6 Å)