ArticleStructure (London, England : 1993)2016
Antibiotic Binding Drives Catalytic Activation of Aminoglycoside Kinase APH(2″)-Ia.
Article in Structure (London, England : 1993), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- Genetic connections and antimicrobial resistance in dogs and ownersFrontiers in veterinary science · 2025Article
- The Peptide Antibiotic Corramycin Adopts a β-Hairpin-like Structure and Is Inactivated by the Kinase ComG.Journal of the American Chemical Society · 2024Article
- Structural basis for the diversity of the mechanism of nucleotide hydrolysis by the aminoglycoside-2''-phosphotransferases.Acta crystallographica. Section D, Structural biology · 2019Article
- 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
- Flipping the Switch "On" for Aminoglycoside-Resistance Enzymes: The Mechanism Is Finally Revealed!Structure (London, England : 1993) · 2016Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
APH(2″)-Ia is a widely disseminated resistance factor frequently found in clinical isolates of Staphylococcus aureus and pathogenic enterococci, where it is constitutively expressed. APH(2″)-Ia confers high-level resistance to gentamicin and related aminoglycosides through phosphorylation of the antibiotic using guanosine triphosphate (GTP) as phosphate donor. We have determined crystal structures of the APH(2″)-Ia in complex with GTP analogs, guanosine diphosphate, and aminoglycosides. These structures collectively demonstrate that aminoglycoside binding to the GTP-bound kinase drives conformational changes that bring distant regions of the protein into contact. These changes in turn drive a switch of the triphosphate cofactor from an inactive, stabilized conformation to a catalytically competent active conformation. This switch has not been previously reported for antibiotic kinases or for the structurally related eukaryotic protein kinases. This catalytic triphosphate switch presents a means by which the enzyme can curtail wasteful hydrolysis of GTP in the absence of aminoglycosides, providing an evolutionary advantage to this enzyme.
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