2-Oxoglutarate (2OG) dependent oxygenases are ubiquitous iron enzymes that couple substrate oxidation to the conversion of 2OG to succinate and carbon dioxide. In humans their roles include collagen biosynthesis, fatty acid metabolism, DNA repair, RNA and chromatin modifications, and hypoxic sensing. Commercial applications of 2OG oxygenase inhibitors began with plant growth retardants, and now extend to a clinically used pharmaceutical compound for cardioprotection. Several 2OG oxygenases are now being targeted for therapeutic intervention for diseases including anaemia, inflammation and cancer. In this critical review, we describe studies on the inhibition of 2OG oxygenases, focusing on small molecules, and discuss the potential of 2OG oxygenases as therapeutic targets (295 references).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1039/c0cs00203h | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Analogue-Sensitive Inhibition of Histone Demethylases Uncovers Member-Specific Function in Ribosomal Protein Synthesis.
J Am Chem Soc
January 2025
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
Lysine demethylases (KDMs) catalyze the oxidative removal of the methyl group from histones using earth-abundant iron and the metabolite 2-oxoglutarate (2OG). KDMs have emerged as master regulators of eukaryotic gene expression and are novel drug targets; small-molecule inhibitors of KDMs are in the clinical pipeline for the treatment of human cancer. Yet, mechanistic insights into the functional heterogeneity of human KDMs are limited, necessitating the development of chemical probes for precision targeting.
View Article and Find Full Text PDFPerformance, kinetics, and mechanism of 1,2,3-trimethylbenzene biodegradation by a newly isolated marine microalga.
J Environ Manage
January 2025
Key Laboratory of Marine Environment and Ecology, Ministry of Education, Ocean University of China, Qingdao, 266100, China; College of Environmental Science and Engineering, Ocean University of China, Qingdao, 266100, China.
Article Synopsis
- Recent marine pollution concerns revolve around the accidental spills of toxic C9 aromatics, particularly 1,2,3-trimethylbenzene (1,2,3-TMB), due to its high toxicity and resistance to degradation.
- A marine diatom, Chaetoceros sp. QG-1, was isolated from Quangang, China, and demonstrated the highest degradation efficiency of 1,2,3-TMB at a concentration of 5 mg/L.
- The study identified the degradation process, where 1,2,3-TMB is converted into less harmful compounds, involving key enzymes like 2OG Fe(II) oxygenase, thus supporting bioremediation efforts in polluted marine environments
How Do Variants of Residues in the First Coordination Sphere, Second Coordination Sphere, and Remote Areas Influence the Catalytic Mechanism of Non-Heme Fe(II)/2-Oxoglutarate Dependent Ethylene-Forming Enzyme?
ACS Catal
December 2024
Department of Chemistry, Michigan Technological University, Houghton, Michigan 49931, United States.
The ethylene-forming enzyme (EFE) is a Fe(II)/2-oxoglutarate (2OG) and l-arginine (l-Arg)-dependent oxygenase that primarily decomposes 2OG into ethylene while also catalyzing l-Arg hydroxylation. While the hydroxylation mechanism in EFE is similar to other Fe(II)/2OG-dependent oxygenases, the formation of ethylene is unique. Various redesign strategies have aimed to increase ethylene production in EFE, but success has been limited, highlighting the need for alternate approaches.
View Article and Find Full Text PDFJmjC catalysed histone H2a N-methyl arginine demethylation and C4-arginine hydroxylation reveals importance of sequence-reactivity relationships.
Commun Biol
November 2024
Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, OX1 3TA, United Kingdom.
2-Oxoglutarate (2OG) dependent N-methyl lysine demethylases (JmjC-KDMs) regulate eukaryotic transcription. We report studies showing that isolated forms of all human KDM4 and KDM5 JmjC enzymes catalyse demethylation of N-methylated Arg-3 of histone H2a. Unexpectedly, the results reveal that KDM4E and, less efficiently, KDM4D catalyse C-4 hydroxylation of Arg-20 of H2a on peptides, recombinant H2a, and calf histone extracts, including when the Arg-20 guanidino group is N-methylated.
View Article and Find Full Text PDFDiscovery and structure-activity relationship study of nicotinamide derivatives as DNA demethylase ALKBH2 inhibitors.
Eur J Med Chem
January 2025
Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 610041, China. Electronic address:
AlkB homolog 2 (ALKBH2) is a Fe (II) and 2-oxoglutarate (2OG)-dependent DNA demethylase. It has been reported to be highly expressed in many cancers including glioblastoma (GBM) and affected disease progression by regulating gene expression. Small molecule inhibitors of ALKBH2 might be used as disease intervention reagents or chemical tools for bio-functional studies of ALKBH2, but currently no potent and selective ALKBH2 inhibitors are reported.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!