ArticleThe Journal of biological chemistry2012
Crystal structure and RNA binding properties of the RNA recognition motif (RRM) and AlkB domains in human AlkB homolog 8 (ABH8), an enzyme catalyzing tRNA hypermodification.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 77 citations in OpenAlex.
- Biological interpretation of DNA/RNA modification by ALKBH proteins and their role in human cancer.European journal of medical research · 2025Review
- ALKBH1: emerging biomarker and therapeutic target for cancer treatment.Discover oncology · 2024Review
- Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family.Current issues in molecular biology · 2024Review
- Structural basis of tRNA recognition by the widespread OB fold.Nature communications · 2024Article
- Recognition of the tRNA structure: Everything everywhere but not all at once.Cell chemical biology · 2024Review
- Structural Basis of Nucleic Acid Recognition and 6mA Demethylation byInternational journal of molecular sciences · 2024Article
- Identification ofFrontiers in plant science · 2024Article
- Article
- RNA methylation in plants: An overview.Frontiers in plant science · 2023Review
- Exploring links between 2-oxoglutarate-dependent oxygenases and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Review
- HITS-CLIP analysis of human ALKBH8 reveals interactions with fully processed substrate tRNAs and with specific noncoding RNAs.RNA (New York, N.Y.) · 2022Article
- Spectroscopic and in vitro Investigations of FeChembiochem : a European journal of chemical biology · 2022Review
- Review
- Epitranscriptomic Reprogramming Is Required to Prevent Stress and Damage from Acetaminophen.Genes · 2022Article
- DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA Dioxygenases.International journal of molecular sciences · 2021Review
- Multi-substrate selectivity based on key loops and non-homologous domains: new insight into ALKBH family.Cellular and molecular life sciences : CMLS · 2021Review
- Mammalian ALKBH1 serves as an NCell research · 2020Article
- N(6)-Methyladenine in eukaryotes.Cellular and molecular life sciences : CMLS · 2019Review
- Recessive Truncating Mutations in ALKBH8 Cause Intellectual Disability and Severe Impairment of Wobble Uridine Modification.American journal of human genetics · 2019Article
- Multi-Substrate Specificity and the Evolutionary Basis for Interdependence in tRNA Editing and Methylation Enzymes.Frontiers in genetics · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Humans express nine paralogs of the bacterial DNA repair enzyme AlkB, an iron/2-oxoglutarate-dependent dioxygenase that reverses alkylation damage to nucleobases. The biochemical and physiological roles of these paralogs remain largely uncharacterized, hampering insight into the evolutionary expansion of the AlkB family. However, AlkB homolog 8 (ABH8), which contains RNA recognition motif (RRM) and methyltransferase domains flanking its AlkB domain, recently was demonstrated to hypermodify the anticodon loops in some tRNAs. To deepen understanding of this activity, we performed physiological and biophysical studies of ABH8. Using GFP fusions, we demonstrate that expression of the Caenorhabditis elegans ABH8 ortholog is widespread in larvae but restricted to a small number of neurons in adults, suggesting that its function becomes more specialized during development. In vitro RNA binding studies on several human ABH8 constructs indicate that binding affinity is enhanced by a basic α-helix at the N terminus of the RRM domain. The 3.0-Å-resolution crystal structure of a construct comprising the RRM and AlkB domains shows disordered loops flanking the active site in the AlkB domain and a unique structural Zn(II)-binding site at its C terminus. Although the catalytic iron center is exposed to solvent, the 2-oxoglutarate co-substrate likely adopts an inactive conformation in the absence of tRNA substrate, which probably inhibits uncoupled free radical generation. A conformational change in the active site coupled to a disorder-to-order transition in the flanking protein segments likely controls ABH8 catalytic activity and tRNA binding specificity. These results provide insight into the functional and structural adaptations underlying evolutionary diversification of AlkB domains.
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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.