ArticleThe Journal of biological chemistry2008
A phospholipid substrate molecule residing in the membrane surface mediates opening of the lid region in group IVA cytosolic phospholipase A2.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- Phospholipases: Where Do We Stand?Methods in molecular biology (Clifton, N.J.) · 2027Review
- Nuciferine Suppresses Inflammatory Hepatocarcinogenesis by Targeting cPLA2-Dependent Arachidonic Acid Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Conformational Dynamics and Activation of Membrane-Associated Human Group IVA Cytosolic Phospholipase AThe journal of physical chemistry letters · 2025Article
- Epigenetic and Metabolic Regulation of Macrophages during Gout.Gout, urate, and crystal deposition disease · 2023Article
- The Phospholipase A2 Superfamily: Structure, Isozymes, Catalysis, Physiologic and Pathologic Roles.International journal of molecular sciences · 2023Review
- Regulatory mechanisms triggered by enzyme interactions with lipid membrane surfaces.Frontiers in molecular biosciences · 2023Review
- Membrane Association Allosterically Regulates Phospholipase AAccounts of chemical research · 2022Article
- Vitamin E functions by association with a novel binding site on the 67 kDa laminin receptor activating diacylglycerol kinase.The Journal of nutritional biochemistry · 2022Article
- Unraveling cardiolipin-induced conformational change of cytochrome c through H/D exchange mass spectrometry and quartz crystal microbalance.Scientific reports · 2021Article
- Lipid-metabolizing serine hydrolases in the mammalian central nervous system: endocannabinoids and beyond.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
- Phospholipase ABiochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
- Structural basis of phosphatidylcholine recognition by the C2-domain of cytosolic phospholipase AeLife · 2019Article
- Dynamic structural biology at the protein membrane interface.The Journal of biological chemistry · 2019Review
- Mitochondrial uncoupling reveals a novel therapeutic opportunity for p53-defective cancers.Nature communications · 2018Article
- The unmasking of the lipid binding face of sphingosine kinase 1.Journal of lipid research · 2018Article
- Molecular mechanism of activation of class IA phosphoinositide 3-kinases (PI3Ks) by membrane-localized HRas.The Journal of biological chemistry · 2017Article
- Liberating Chiral Lipid Mediators, Inflammatory Enzymes, and LIPID MAPS from Biological Grease.The Journal of biological chemistry · 2016Review
- Computer-aided drug design guided by hydrogen/deuterium exchange mass spectrometry: A powerful combination for the development of potent and selective inhibitors of Group VIA calcium-independent phospholipase ABioorganic & medicinal chemistry · 2016Article
- Membrane and inhibitor interactions of intracellular phospholipases A2.Advances in biological regulation · 2016Review
- Cytosolic phospholipase A₂: physiological function and role in disease.Journal of lipid research · 2015Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The Group IVA (GIVA) phospholipase A(2) associates with natural membranes in response to an increase in intracellular Ca(2+) along with increases in certain lipid mediators. This enzyme associates with the membrane surface as well as binding a single phospholipid molecule in the active site for catalysis. Employing deuterium exchange mass spectrometry, we have identified the regions of the protein binding the lipid surface and conformational changes upon a single phospholipid binding in the absence of a lipid surface. Experiments were carried out using natural palmitoyl arachidonyl phosphatidylcholine vesicles with the intact GIVA enzyme as well as the isolated C2 and catalytic domains. Lipid binding produced changes in deuterium exchange in eight different regions of the protein. The regions with decreased exchange included Ca(2+) binding loop one, which has been proposed to penetrate the membrane surface, and a charged patch of residues, which may be important in interacting with the polar head groups of phospholipids. The regions with an increase in exchange are all located either in the hydrophobic core underneath the lid region or near the lid and hinge regions from 403 to 457. Using the GIVA phospholipase A(2) irreversible inhibitor methyl-arachidonyl fluorophosphonate, we were able to isolate structural changes caused only by pseudo-substrate binding. This produced results that were very similar to natural lipid binding in the presence of a lipid interface with the exception of the C2 domain and region 466-470. This implies that most of the changes seen in the catalytic domain are due to a substrate-mediated, not interface-mediated, lid opening, which exposes the active site to water. Finally experiments carried out with inhibitor plus phospholipid vesicles showed decreases at the C2 domain as well as charged residues on the putative membrane binding surface of the catalytic domain revealing the binding sites of the enzyme to the lipid surface.
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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.