ArticleProceedings of the National Academy of Sciences of the United States of America2011
Unusual regioversatility of acetyltransferase Eis, a cause of drug resistance in XDR-TB.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- Transcriptional Profiling of Mycobacterium tuberculosis Exposed to In Vitro Lysosomal Stress.Infection and immunity · 2016Pooled it
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- NProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Overcoming aminoglycoside antibiotic resistance inIn silico pharmacology · 2025Article
- Microevolutionary models and multi-omics analysis uncover the cross-drug resistance characteristics of capreomycin-selectedCurrent research in microbial sciences · 2025Article
- Newly Identified Mycobacterium africanum Lineage 10, Central Africa.Emerging infectious diseases · 2024Article
- Bacterial protein acetylation: mechanisms, functions, and methods for study.Frontiers in cellular and infection microbiology · 2024Review
- Restoring susceptibility to aminoglycosides: identifying small molecule inhibitors of enzymatic inactivation.RSC medicinal chemistry · 2023Review
- Analysis of Genome-Wide Mutational Dependence in Naturally Evolving Mycobacterium tuberculosis Populations.Molecular biology and evolution · 2023Article
- The implication of Mycobacterium tuberculosis-mediated metabolism of targeted xenobiotics.Nature reviews. Chemistry · 2023Review
- Discovery and Mechanistic Analysis of Structurally Diverse Inhibitors of Acetyltransferase Eis among FDA-Approved Drugs.Biochemistry · 2023Article
- Discovery and development of inhibitors of acetyltransferase Eis to combat Mycobacterium tuberculosis.Methods in enzymology · 2023Article
- The role of adjuvants in overcoming antibacterial resistance due to enzymatic drug modification.RSC medicinal chemistry · 2022Review
- Discovery of substituted benzyloxy-benzylamine inhibitors of acetyltransferase Eis and their anti-mycobacterial activity.European journal of medicinal chemistry · 2022Article
- Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year's review.BMC infectious diseases · 2022Article
- Structure-based design of haloperidol analogues as inhibitors of acetyltransferase Eis fromRSC medicinal chemistry · 2021Article
- Structural characterization of a GNAT family acetyltransferase from Elizabethkingia anophelis bound to acetyl-CoA reveals a new dimeric interface.Scientific reports · 2021Article
- Post-translational Lysine Ac(et)ylation in Bacteria: A Biochemical, Structural, and Synthetic Biological Perspective.Frontiers in microbiology · 2021Review
- Mechanisms of Drug-Induced Tolerance in Mycobacterium tuberculosis.Clinical microbiology reviews · 2020Review
- Structure-Guided Optimization of Inhibitors of Acetyltransferase Eis fromACS chemical biology · 2020Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emergence of multidrug-resistant and extensively drug-resistant (XDR) tuberculosis (TB) is a serious global threat. Aminoglycoside antibiotics are used as a last resort to treat XDR-TB. Resistance to the aminoglycoside kanamycin is a hallmark of XDR-TB. Here, we reveal the function and structure of the mycobacterial protein Eis responsible for resistance to kanamycin in a significant fraction of kanamycin-resistant Mycobacterium tuberculosis clinical isolates. We demonstrate that Eis has an unprecedented ability to acetylate multiple amines of many aminoglycosides. Structural and mutagenesis studies of Eis indicate that its acetylation mechanism is enabled by a complex tripartite fold that includes two general control non-derepressible 5 (GCN5)-related N-acetyltransferase regions. An intricate negatively charged substrate-binding pocket of Eis is a potential target of new antitubercular drugs expected to overcome aminoglycoside 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.