ArticleActa crystallographica. Section D, Biological crystallography2014
Structure of the bifunctional aminoglycoside-resistance enzyme AAC(6')-Ie-APH(2'')-Ia revealed by crystallographic and small-angle X-ray scattering analysis.
Article in Acta crystallographica. Section D, Biological crystallography, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- APH Inhibitors that Reverse Aminoglycoside Resistance in Enterococcus casseliflavus.ChemMedChem · 2025Article
- Proteomics and metabolomics analyses of Streptococcus agalactiae isolates from human and animal sources.Scientific reports · 2023Article
- N-Formimidoylation/-iminoacetylation modification in aminoglycosides requires FAD-dependent and ligand-protein NOS bridge dual chemistry.Nature communications · 2023Article
- Unusual peptide-binding proteins guide pyrroloindoline alkaloid formation in crocagin biosynthesis.Nature chemistry · 2023Article
- Structural and phylogenetic analyses of resistance to next-generation aminoglycosides conferred by AAC(2') enzymes.Scientific reports · 2021Article
- Plasticity of Aminoglycoside Binding to Antibiotic Kinase APH(2″)-Ia.Antimicrobial agents and chemotherapy · 2018Article
- Comprehensive review of chemical strategies for the preparation of new aminoglycosides and their biological activities.Chemical Society reviews · 2018Review
- Amikacin: Uses, Resistance, and Prospects for Inhibition.Molecules (Basel, Switzerland) · 2017Review
- Aminoglycoside resistance profile and structural architecture of the aminoglycoside acetyltransferase AAC(6')-Im.Microbial cell (Graz, Austria) · 2017Article
- Expanding Aminoglycoside Resistance Enzyme Regiospecificity by Mutation and Truncation.Biochemistry · 2016Article
- Flipping the Switch "On" for Aminoglycoside-Resistance Enzymes: The Mechanism Is Finally Revealed!Structure (London, England : 1993) · 2016Article
- Structure and Functional Diversity of GCN5-Related N-Acetyltransferases (GNAT).International journal of molecular sciences · 2016Review
- Bacterial GCN5-Related N-Acetyltransferases: From Resistance to Regulation.Biochemistry · 2016Review
- Mechanisms of Resistance to Aminoglycoside Antibiotics: Overview and Perspectives.MedChemComm · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
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Abstract
Broad-spectrum resistance to aminoglycoside antibiotics in clinically important Gram-positive staphylococcal and enterococcal pathogens is primarily conferred by the bifunctional enzyme AAC(6')-Ie-APH(2'')-Ia. This enzyme possesses an N-terminal coenzyme A-dependent acetyltransferase domain [AAC(6')-Ie] and a C-terminal GTP-dependent phosphotransferase domain [APH(2'')-Ia], and together they produce resistance to almost all known aminoglycosides in clinical use. Despite considerable effort over the last two or more decades, structural details of AAC(6')-Ie-APH(2'')-Ia have remained elusive. In a recent breakthrough, the structure of the isolated C-terminal APH(2'')-Ia enzyme was determined as the binary Mg2GDP complex. Here, the high-resolution structure of the N-terminal AAC(6')-Ie enzyme is reported as a ternary kanamycin/coenzyme A abortive complex. The structure of the full-length bifunctional enzyme has subsequently been elucidated based upon small-angle X-ray scattering data using the two crystallographic models. The AAC(6')-Ie enzyme is joined to APH(2'')-Ia by a short, predominantly rigid linker at the N-terminal end of a long α-helix. This α-helix is in turn intrinsically associated with the N-terminus of APH(2'')-Ia. This structural arrangement supports earlier observations that the presence of the intact α-helix is essential to the activity of both functionalities of the full-length AAC(6')-Ie-APH(2'')-Ia enzyme.
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