ArticleBiochemistry2015
Identification of the Substrate Access Portal of 5-Lipoxygenase.
Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 34 citations in OpenAlex.
- Dual synergistic inhibition of COX and LOX by potential chemicals from Indian daily spices investigated through detailed computational studies.Scientific reports · 2023Article
- Untangling the web of 5-lipoxygenase-derived products from a molecular and structural perspective: The battle between pro- and anti-inflammatory lipid mediators.Biochemical pharmacology · 2021Review
- Potential Anticancer Lipoxygenase Inhibitors from the Red Sea-Derived Brown AlgaeAntibiotics (Basel, Switzerland) · 2021Article
- Lipoxygenase catalyzed metabolites derived from docosahexaenoic acid are promising antitumor agents against breast cancer.Scientific reports · 2021Article
- New Zileuton-Hydroxycinnamic Acid Hybrids: Synthesis and Structure-Activity Relationship towards 5-Lipoxygenase Inhibition.Molecules (Basel, Switzerland) · 2020Article
- Fatty Acid Allosteric Regulation of C-H Activation in Plant and Animal Lipoxygenases.Molecules (Basel, Switzerland) · 2020Review
- A site-moiety map and virtual screening approach for discovery of novel 5-LOX inhibitors.Scientific reports · 2020Article
- The role of propofol hydroxyl group in 5-lipoxygenase recognition.Biochemical and biophysical research communications · 2020Article
- Biological Properties and Absolute Configuration of Flavanones FromFrontiers in pharmacology · 2020Article
- Phenolic acid phenethylesters and their corresponding ketones: Inhibition of 5-lipoxygenase and stability in human blood and HepaRG cells.Pharmacology research & perspectives · 2019Article
- Leukotriene biosynthetic enzymes as therapeutic targets.The Journal of clinical investigation · 2018Review
- Intravenous anesthetic propofol binds to 5-lipoxygenase and attenuates leukotriene BFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- 5-Lipoxygenase-activating protein rescues activity of 5-lipoxygenase mutations that delay nuclear membrane association and disrupt product formation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The overproduction of inflammatory lipid mediators derived from arachidonic acid contributes to asthma and cardiovascular diseases, among other pathologies. Consequently, the enzyme that initiates the synthesis of pro-inflammatory leukotrienes, 5-lipoxygenase (5-LOX), is a target for drug design. The crystal structure of 5-LOX revealed a fully encapsulated active site; thus the point of substrate entry is not known. We asked whether a structural motif, a "cork" present in 5-LOX but absent in other mammalian lipoxygenases, might be ejected to allow substrate access. Our results indicate that reduction of cork volume facilitates access to the active site. However, if cork entry into the site is obstructed, enzyme activity is significantly compromised. The results support a model in which the "cork" that shields the active site in the absence of substrate serves as the active site portal, but the "corking" amino acid Phe-177 plays a critical role in providing a fully functional active site. Thus, the more appropriate metaphor for this structural motif is a "twist-and-pour" cap. Additional mutagenesis data are consistent with a role for His-600, deep in the elongated cavity, in positioning the substrate for catalysis.
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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.