ArticleAntimicrobial agents and chemotherapy2012
Small-angle X-ray scattering analysis of the bifunctional antibiotic resistance enzyme aminoglycoside (6') acetyltransferase-ie/aminoglycoside (2'') phosphotransferase-ia reveals a rigid solution structure.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- 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
- Aminoglycoside resistance profile and structural architecture of the aminoglycoside acetyltransferase AAC(6')-Im.Microbial cell (Graz, Austria) · 2017Article
- Sulfonamide-Based Inhibitors of Aminoglycoside Acetyltransferase Eis Abolish Resistance to Kanamycin in Mycobacterium tuberculosis.Journal of medicinal chemistry · 2016Article
- Flipping the Switch "On" for Aminoglycoside-Resistance Enzymes: The Mechanism Is Finally Revealed!Structure (London, England : 1993) · 2016Article
- Potent Inhibitors of Acetyltransferase Eis Overcome Kanamycin Resistance in Mycobacterium tuberculosis.ACS chemical biology · 2016Article
- Mechanisms of Resistance to Aminoglycoside Antibiotics: Overview and Perspectives.MedChemComm · 2016Article
- Arginine-linked neomycin B dimers: synthesis, rRNA binding, and resistance enzyme activity.MedChemComm · 2016Article
- Inhibition of aminoglycoside acetyltransferase resistance enzymes by metal salts.Antimicrobial agents and chemotherapy · 2015Article
- Structure of the bifunctional aminoglycoside-resistance enzyme AAC(6')-Ie-APH(2'')-Ia revealed by crystallographic and small-angle X-ray scattering analysis.Acta crystallographica. Section D, Biological crystallography · 2014Article
- Structure of the phosphotransferase domain of the bifunctional aminoglycoside-resistance enzyme AAC(6')-Ie-APH(2'')-Ia.Acta crystallographica. Section D, Biological crystallography · 2014Article
- Strategies to overcome the action of aminoglycoside-modifying enzymes for treating resistant bacterial infections.Future medicinal chemistry · 2013Review
- Domain dissection and characterization of the aminoglycoside resistance enzyme ANT(3″)-Ii/AAC(6')-IId from Serratia marcescens.Biochimie · 2013Article
- Prospects for circumventing aminoglycoside kinase mediated antibiotic resistance.Frontiers in cellular and infection microbiology · 2013Review
- Cosubstrate tolerance of the aminoglycoside resistance enzyme Eis from Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2012Article
- A review of patents (2011-2015) towards combating resistance to and toxicity of aminoglycosides.MedChemCommArticle
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2 authors at 1 institution in 1 country.
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Abstract
Aminoglycoside (6') acetyltransferase-Ie/aminoglycoside (2″) phosphotransferase-Ia [AAC(6')-Ie/APH(2″)-Ia] is one of the most problematic aminoglycoside resistance factors in clinical pathogens, conferring resistance to almost every aminoglycoside antibiotic available to modern medicine. Despite 3 decades of research, our understanding of the structure of this bifunctional enzyme remains limited. We used small-angle X-ray scattering (SAXS) to model the structure of this bifunctional enzyme in solution and to study the impact of substrate binding on the enzyme. It was observed that the enzyme adopts a rigid conformation in solution, where the N-terminal AAC domain is fixed to the C-terminal APH domain and not loosely tethered. The addition of acetyl-coenzyme A, coenzyme A, GDP, guanosine 5'-[β,γ-imido]triphosphate (GMPPNP), and combinations thereof to the protein resulted in only modest changes to the radius of gyration (R(G)) of the enzyme, which were not consistent with any large changes in enzyme structure upon binding. These results imply some selective advantage to the bifunctional enzyme beyond coexpression as a single polypeptide, likely linked to an improvement in enzymatic properties. We propose that the rigid structure contributes to improved electrostatic steering of aminoglycoside substrates toward the two active sites, which may provide such an advantage.
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