6vta | pdb_00006vta

Aminoglycoside N-2'-Acetyltransferase-Ia [AAC(2')-Ia] in complex with amikacin and acetyl-CoA

spinqualitylabelsall models 6vta, resolution 1.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6vta is a 2 chain structure with sequence from Providencia stuartii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.42Å Ligands: ACO, AKN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AAC2_PROST Publication Abstract from PubMed Plazomicin is currently the only next-generation aminoglycoside approved for clinical use that has the potential of evading the effects of widespread enzymatic resistance factors. However, plazomicin is still susceptible to the action of the resistance enzyme AAC(2')-Ia from Providencia stuartii. As the clinical use of plazomicin begins to increase, the spread of resistance factors will undoubtedly accelerate, rendering this aminoglycoside increasingly obsolete. Understanding resistance to plazomicin is an important step to ensure this aminoglycoside remains a viable treatment option for the foreseeable future. Here, we present three crystal structures of AAC(2')-Ia from P. stuartii, two in complex with acetylated aminoglycosides tobramycin and netilmicin, and one in complex with a non-substrate aminoglycoside, amikacin. Together, with our previously reported AAC(2')-Ia-acetylated plazomicin complex, these structures outline AAC(2')-Ia's specificity for a wide range of aminoglycosides. Additionally, our survey of AAC(2')-I homologues highlights the conservation of residues predicted to be involved in aminoglycoside binding, and identifies the presence of plasmid-encoded enzymes in environmental strains that confer resistance to the latest next-generation aminoglycoside. These results forecast the likely spread of plazomicin resistance and highlight the urgency for advancements in next-generation aminoglycoside design. Structural and phylogenetic analyses of resistance to next-generation aminoglycosides conferred by AAC(2') enzymes.,Bassenden AV, Dumalo L, Park J, Blanchet J, Maiti K, Arya DP, Berghuis AM Sci Rep. 2021 Jun 2;11(1):11614. doi: 10.1038/s41598-021-89446-3. PMID:34078922 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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