ArticleThe EMBO journal2002
Substrate promiscuity of an aminoglycoside antibiotic resistance enzyme via target mimicry.
Article in The EMBO journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 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
64 citing papers in PubMed, 158 citations in OpenAlex.
- Comparative Analysis of AlphaFold2 Models and Intrinsic Disorder Illuminates Structural Divergence as a Symptom of Functional Divergence Across the Calmodulin Superfamily.Journal of molecular evolution · 2026Article
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Pseudokinases can catalyse peptide cyclization through thioether crosslinking.Nature chemistry · 2026Article
- Enzyme-mediated aminoglycoside resistance without target mimicry.Communications chemistry · 2025Article
- APH Inhibitors that Reverse Aminoglycoside Resistance in Enterococcus casseliflavus.ChemMedChem · 2025Article
- Architecture, Function, Regulation, and Evolution of α-Glucans Metabolic Enzymes in Prokaryotes.Chemical reviews · 2024Review
- Frankincense (Current issues in molecular biology · 2024Article
- APH(3')-Ie, an aminoglycoside-modifying enzyme discovered in a rabbit-derivedFrontiers in cellular and infection microbiology · 2024Article
- Discovery and characterization of genes conferring natural resistance to the antituberculosis antibiotic capreomycin.Communications biology · 2023Article
- Tree visualizations of protein sequence embedding space enable improved functional clustering of diverse protein superfamilies.Briefings in bioinformatics · 2023Article
- Late-Stage Modification of Aminoglycoside Antibiotics Overcomes Bacterial Resistance Mediated by APH(3') Kinases.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Amphiphilic aminoglycosides: Modifications that revive old natural product antibiotics.Frontiers in microbiology · 2022Review
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- Antibiotic resistance in agriculture: Perspectives on upcoming strategies to overcome upsurge in resistance.Current research in microbial sciences · 2021Review
- Structural basis for plazomicin antibiotic action and resistance.Communications biology · 2021Article
- Structural and phylogenetic analyses of resistance to next-generation aminoglycosides conferred by AAC(2') enzymes.Scientific reports · 2021Article
- A redox-active switch in fructosamine-3-kinases expands the regulatory repertoire of the protein kinase superfamily.Science signaling · 2020Article
- Drug Resistance and the Prevention Strategies in Food Borne Bacteria: An Update Review.Advanced pharmaceutical bulletin · 2019Review
- Investigating the promiscuity of the chloramphenicol nitroreductase from Haemophilus influenzae towards the reduction of 4-nitrobenzene derivatives.Bioorganic & medicinal chemistry letters · 2019Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The misuse of antibiotics has selected for bacteria that have evolved mechanisms for evading the effects of these drugs. For aminoglycosides, a group of clinically important bactericidal antibiotics that target the A-site of the 16S ribosomal RNA, the most common mode of resistance is enzyme-catalyzed chemical modification of the drug. While aminoglycosides are structurally diverse, a single enzyme can confer resistance to many of these antibiotics. For example, the aminoglycoside kinase APH(3')-IIIa, produced by pathogenic Gram-positive bacteria such as enterococci and staphylococci, is capable of detoxifying at least 10 distinct aminoglycosides. Here we describe the crystal structures of APH(3')-IIIa in complex with ADP and kanamycin A or neomycin B. These structures reveal that the basis for this enzyme's substrate promiscuity is the presence of two alternative subsites in the antibiotic binding pocket. Furthermore, comparison between the A-site of the bacterial ribosome and APH(3')-IIIa shows that mimicry is the second major factor in dictating the substrate spectrum of APH(3')-IIIa. These results suggest a potential strategy for drug design aimed at circumventing antibiotic resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.