ArticleJournal of molecular biology2010
Crystal structure of fatty acid amide hydrolase bound to the carbamate inhibitor URB597: discovery of a deacylating water molecule and insight into enzyme inactivation.
Article in Journal of molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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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
45 citing papers in PubMed, 105 citations in OpenAlex.
- Identification of quinolinyl-containing dual soluble epoxide hydrolase/fatty acid amide hydrolase inhibitors with moderate potency towards acetylcholinesterase.Results in chemistry · 2026Article
- Toward a Better Understanding of Fatty Acid Amide Hydrolase Inhibition by β-Lactams.Chemistry & biodiversity · 2026Article
- Structure-activity relationship studies and pharmacological evaluation of 4-phenylthiazoles as dual soluble epoxide hydrolase/fatty acid amide hydrolase inhibitors.Bioorganic & medicinal chemistry · 2025Article
- Promising Inhibitors of Endocannabinoid Degrading Enzymes Sharing a Carbamate Scaffold.Mini reviews in medicinal chemistry · 2025Review
- Article
- Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years.Pharmacological reviews · 2023Review
- Two legume fatty acid amide hydrolase isoforms with distinct preferences for microbial- and plant-derived acylamides.Scientific reports · 2023Article
- Advanced Pyrrolidine-Carbamate Self-Immolative Spacer with Tertiary Amine Handle Induces Superfast Cyclative Drug Release.ChemMedChem · 2022Article
- Identifying FAAH Inhibitors as New Therapeutic Options for the Treatment of Chronic Pain through Drug Repurposing.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Further exploration of the structure-activity relationship of dual soluble epoxide hydrolase/fatty acid amide hydrolase inhibitors.Bioorganic & medicinal chemistry · 2021Article
- New Coumarin Derivatives as Cholinergic and Cannabinoid System Modulators.Molecules (Basel, Switzerland) · 2021Article
- Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System.International journal of molecular sciences · 2021Review
- Fatty acid amide hydrolase is lower in young cannabis users.Addiction biology · 2021Article
- The endocannabinoid hydrolase FAAH is an allosteric enzyme.Scientific reports · 2020Article
- Modulation of Pain Sensitivity by Chronic Consumption of Highly Palatable Food Followed by Abstinence: Emerging Role of Fatty Acid Amide Hydrolase.Frontiers in pharmacology · 2020Article
- Pharmacokinetics, pharmacodynamics and safety studies on URB937, a peripherally restricted fatty acid amide hydrolase inhibitor, in rats.The Journal of pharmacy and pharmacology · 2019Article
- Discovery of a Potent, Long-Acting, and CNS-Active Inhibitor (BIA 10-2474) of Fatty Acid Amide Hydrolase.ChemMedChem · 2018Article
- Dual cyclooxygenase-fatty acid amide hydrolase inhibitor exploits novel binding interactions in the cyclooxygenase active site.The Journal of biological chemistry · 2018Article
- Development of terphenyl-2-methyloxazol-5(4H)-one derivatives as selective reversible MAGL inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2017Article
- Human serine racemase structure/activity relationship studies provide mechanistic insight and point to position 84 as a hot spot for β-elimination function.The Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The endocannabinoid system regulates a wide range of physiological processes including pain, inflammation, and cognitive/emotional states. URB597 is one of the best characterized covalent inhibitors of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH). Here, we report the structure of the FAAH-URB597 complex at 2.3 A resolution. The structure provides insights into mechanistic details of enzyme inactivation and experimental evidence of a previously uncharacterized active site water molecule that likely is involved in substrate deacylation. This water molecule is part of an extensive hydrogen-bonding network and is coordinated indirectly to residues lining the cytosolic port of the enzyme. In order to corroborate our hypothesis concerning the role of this water molecule in FAAH's catalytic mechanism, we determined the structure of FAAH conjugated to a urea-based inhibitor, PF-3845, to a higher resolution (2.4 A) than previously reported. The higher-resolution structure confirms the presence of the water molecule in a virtually identical location in the active site. Examination of the structures of serine hydrolases that are non-homologous to FAAH, such as elastase, trypsin, or chymotrypsin, shows a similarly positioned hydrolytic water molecule and suggests a functional convergence between the amidase signature enzymes and serine proteases.
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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.