ArticleThe Journal of biological chemistry2011
Human cyclooxygenase-2 is a sequence homodimer that functions as a conformational heterodimer.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 113 citations in OpenAlex.
- Prostaglandins: Key players in immunomodulation of the nervous system.Neural regeneration research · 2026Article
- The role of prostanoids in the retina and optic nerve in health and disease.Progress in retinal and eye research · 2026Review
- RIPK1 ubiquitination regulates its kinase-independent function in development and inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Allosteric regulation of prostaglandin endoperoxide HThe Journal of biological chemistry · 2025Review
- Activity-dependent COX-2 proteolysis modulates aerobic respiration and proliferation in a prostaglandin-independent manner.iScience · 2024Article
- Exploration of bioactive compounds from3 Biotech · 2024Article
- Defining the Conformational Ensembles Associated with Ligand Binding to Cyclooxygenase-2.Biochemistry · 2023Article
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- Puerarin Alleviates Depression-Like Behavior Induced by High-Fat Diet Combined With Chronic Unpredictable Mild StressFrontiers in pharmacology · 2021Article
- Harmaline Analogs as Substrate-Selective Cyclooxygenase-2 Inhibitors.ACS medicinal chemistry letters · 2020Article
- Structural and Chemical Biology of the Interaction of Cyclooxygenase with Substrates and Non-Steroidal Anti-Inflammatory Drugs.Chemical reviews · 2020Review
- The Biosynthesis of Enzymatically Oxidized Lipids.Frontiers in endocrinology · 2020Review
- A New Look at the Structures of Old Sepsis Actors by Exploratory Data Analysis Tools.Antibiotics (Basel, Switzerland) · 2019Article
- Arg-513 and Leu-531 Are Key Residues Governing Time-Dependent Inhibition of Cyclooxygenase-2 by Aspirin and Celebrex.Biochemistry · 2019Article
- Increases in Colonic Bacterial Diversity after ω-3 Fatty Acid Supplementation Predict Decreased Colonic Prostaglandin E2 Concentrations in Healthy Adults.The Journal of nutrition · 2019Article
- A seven-step plan for becoming a moderately rich and famous biochemist.The Journal of biological chemistry · 2019Article
- Interactions of fatty acids, nonsteroidal anti-inflammatory drugs, and coxibs with the catalytic and allosteric subunits of cyclooxygenases-1 and -2.The Journal of biological chemistry · 2019Review
- Signal integration and information transfer in an allosterically regulated network.NPJ systems biology and applications · 2019Article
- Investigating the Connection Between Endogenous Heme Accumulation and COX2 Activity in Cancer Cells.Frontiers in oncology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Prostaglandin endoperoxide H synthases 1 and 2, also known as cyclooxygenases (COXs) 1 and 2, convert arachidonic acid (AA) to prostaglandin endoperoxide H(2). Prostaglandin endoperoxide H synthases are targets of nonspecific nonsteroidal anti-inflammatory drugs and COX-2-specific inhibitors called coxibs. PGHS-2 is a sequence homodimer. Each monomer has a peroxidase and a COX active site. We find that human PGHS-2 functions as a conformational heterodimer having a catalytic monomer (E(cat)) and an allosteric monomer (E(allo)). Heme binds tightly only to the peroxidase site of E(cat), whereas substrates, as well as certain inhibitors (e.g. celecoxib), bind the COX site of E(cat). E(cat) is regulated by E(allo) in a manner dependent on what ligand is bound to E(allo). Substrate and nonsubstrate fatty acids (FAs) and some COX inhibitors (e.g. naproxen) preferentially bind to the COX site of E(allo). AA can bind to E(cat) and E(allo), but the affinity of AA for E(allo) is 25 times that for E(cat). Palmitic acid, an efficacious stimulator of human PGHS-2, binds only E(allo) in palmitic acid/murine PGHS-2 co-crystals. Nonsubstrate FAs can potentiate or attenuate actions of COX inhibitors depending on the FA and whether the inhibitor binds E(cat) or E(allo). Our studies suggest that the concentration and composition of the free FA pool in the environment in which PGHS-2 functions in cells, the FA tone, is a key factor regulating PGHS-2 activity and its responses to COX inhibitors. We suggest that differences in FA tone occurring with different diets will likely affect both base-line prostanoid synthesis and responses to COX inhibitors.
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What OpenQuestion holds
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.