ArticleNucleic acids research2014
Structure of human RNA N⁶-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 1 of them a synthesis that pooled it.
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Who cites it
142 citing papers in PubMed, 1 synthesis or guideline pooled it, 247 citations in OpenAlex.
- Role of N6-Methyladenosine Methylation Regulators in the Drug Therapy of Digestive System Tumours.Frontiers in pharmacology · 2022Pooled it
- How Epitranscriptomic Machinery Senses Environmental Cues.Advanced biology · 2026Review
- Functional Role of ALKBH5 in Kidney Injury: Insights Into Mechanisms and Therapeutic Potential.Journal of cellular biochemistry · 2026Review
- Article
- Genome-Wide Characterization of theGenes · 2026Article
- The Role of NMedComm · 2026Review
- The role of m6A modification in spermatogenic dysfunction.Molecular biology reports · 2026Review
- Metabolic oxidoreductases: central regulators of the epigenetic landscapes in stemness.Experimental & molecular medicine · 2026Review
- The N6-Methyladenosine RNA Demethylase AlkB Homolog 5 (ALKBH5) in Metabolic Diseases: Molecular Mechanisms and Pharmacological Implications-A Review.Biomolecules · 2026Review
- Structure-based Discovery of a Non-competitive FTO Inhibitor Bound to a Cryptic Site at the Domain Interface.Journal of molecular biology · 2026Article
- ALKBH5 inhibitors for cancer therapy: molecular docking, challenges and future prospects.Frontiers in pharmacology · 2026Review
- The role of mGenes & diseases · 2026Review
- Context-dependent functions of ALKBH5: a mechanistic framework linking cellular stress responses, immune regulation, viral infection, and therapeutic vulnerabilities.Frontiers in immunology · 2026Review
- RNA methylation modifications in neurodegenerative diseases: Focus on their enzyme system.Journal of advanced research · 2025Review
- Targeting RNA adenosine editing and modification enzymes for RNA therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Evidence human FTO catalyses hydroxylation of N6-methyladenosine without direct formation of a demethylated product contrasting with ALKBH5/2/3 and bacterial AlkB.Nucleic acids research · 2025Article
- Revealing the catalytic mechanism of the Fe(II)/2-oxoglutarate-dependent human epigenetic modifying enzyme ALKBH5.Cell reports. Physical science · 2025Article
- Catalytic Mechanism of the Bacterial Non-Heme Fe(II) and 2-Oxoglutarate Dependent Enzyme AlkB with Single-Stranded DNA Containing Complex Guanine Adducts.Inorganic chemistry · 2025Article
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82 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
ALKBH5 is a 2-oxoglutarate (2OG) and ferrous iron-dependent nucleic acid oxygenase (NAOX) that catalyzes the demethylation of N(6)-methyladenine in RNA. ALKBH5 is upregulated under hypoxia and plays a role in spermatogenesis. We describe a crystal structure of human ALKBH5 (residues 66-292) to 2.0 Å resolution. ALKBH5₆₆₋₂₉₂ has a double-stranded β-helix core fold as observed in other 2OG and iron-dependent oxygenase family members. The active site metal is octahedrally coordinated by an HXD…H motif (comprising residues His204, Asp206 and His266) and three water molecules. ALKBH5 shares a nucleotide recognition lid and conserved active site residues with other NAOXs. A large loop (βIV-V) in ALKBH5 occupies a similar region as the L1 loop of the fat mass and obesity-associated protein that is proposed to confer single-stranded RNA selectivity. Unexpectedly, a small molecule inhibitor, IOX3, was observed covalently attached to the side chain of Cys200 located outside of the active site. Modelling substrate into the active site based on other NAOX-nucleic acid complexes reveals conserved residues important for recognition and demethylation mechanisms. The structural insights will aid in the development of inhibitors selective for NAOXs, for use as functional probes and for therapeutic benefit.
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Registered trials
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