7lap | pdb_00007lap

Crystal structure of aminoglycoside acetyltransferase AAC(3)-Xa

spinqualitylabelsall models 7lap, resolution 2.04Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7lap is a 2 chain structure with sequence from "actinomyces_griseus"_krainsky_1914 "actinomyces griseus" krainsky 1914. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, FMT, TAR Gene: kan, yokD_2, NCTC13033_06639 ("Actinomyces griseus" Krainsky 1914) Activity: Aminoglycoside N(3')-acetyltransferase, with EC number 2.3.1.81 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The environmental microbiome harbors a vast repertoire of antibiotic resistance genes (ARGs) which can serve as evolutionary predecessors for ARGs found in pathogenic bacteria, or can be directly mobilized to pathogens in the presence of selection pressures. Thus, ARGs from benign environmental bacteria are an important resource for understanding clinically relevant resistance. Here, we conduct a comprehensive functional analysis of the Antibiotic_NAT family of aminoglycoside acetyltransferases. We determined a pan-family antibiogram of 21 Antibiotic_NAT enzymes, including 8 derived from clinical isolates and 13 from environmental metagenomic samples. We find that environment-derived representatives confer high-level, broad-spectrum resistance, including against the atypical aminoglycoside apramycin, and that a metagenome-derived gene likely is ancestral to an aac(3) gene found in clinical isolates. Through crystallographic analysis, we rationalize the molecular basis for diversification of substrate specificity across the family. This work provides critical data on the molecular mechanism underpinning resistance to established and emergent aminoglycoside antibiotics and broadens our understanding of ARGs in the environment. Structural and molecular rationale for the diversification of resistance mediated by the Antibiotic_NAT family.,Stogios PJ, Bordeleau E, Xu Z, Skarina T, Evdokimova E, Chou S, Diorio-Toth L, D'Souza AW, Patel S, Dantas G, Wright GD, Savchenko A Commun Biol. 2022 Mar 25;5(1):263. doi: 10.1038/s42003-022-03219-w. PMID:35338238 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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