5f48

Crystal structure of an aminoglycoside acetyltransferase meta-AAC0020 from an uncultured soil metagenomic sample in complex with coenzyme A

spinqualitylabelsall models 5f48, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5f48 is a 2 chain structure with sequence from Uncultured bacterium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: CL, COA, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A059WZ16_9BACT Publication Abstract from PubMed Aminoglycoside N-acetyltransferases (AACs) confer resistance against the clinical use of aminoglycoside antibiotics. The origin of AACs can be traced to environmental microbial species representing a vast reservoir for new and emerging resistance enzymes, which are currently undercharacterized. Here, we performed detailed structural characterization and functional analyses of four metagenomic AAC (meta-AACs) enzymes recently identified in a survey of agricultural and grassland soil microbiomes ( Forsberg et al. Nature 2014 , 509 , 612 ). These enzymes are new members of the Gcn5-Related-N-Acetyltransferase superfamily and confer resistance to the aminoglycosides gentamicin C, sisomicin, and tobramycin. Moreover, the meta-AAC0020 enzyme demonstrated activity comparable with an AAC(3)-I enzyme that serves as a model AAC enzyme identified in a clinical bacterial isolate. The crystal structure of meta-AAC0020 in complex with sisomicin confirmed an unexpected AAC(6') regiospecificity of this enzyme and revealed a drug binding mechanism distinct from previously characterized AAC(6') enzymes. Together, our data highlights the presence of highly active antibiotic-modifying enzymes in the environmental microbiome and reveals unexpected diversity in substrate specificity. These observations of additional AAC enzymes must be considered in the search for novel aminoglycosides less prone to resistance. Structural and Functional Survey of Environmental Aminoglycoside Acetyltransferases Reveals Functionality of Resistance Enzymes.,Xu Z, Stogios PJ, Quaile AT, Forsberg KJ, Patel S, Skarina T, Houliston S, Arrowsmith C, Dantas G, Savchenko A ACS Infect Dis. 2017 Sep 8;3(9):653-665. doi: 10.1021/acsinfecdis.7b00068. Epub, 2017 Aug 16. PMID:28756664 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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