BIOMAT Database Logo BIOMAT Database Logo

Molecular basis of phospholipase A2 activity toward phospholipids with sn-1 substitutions. 2008

Lars Linderoth, and Thomas L Andresen, and Kent Jørgensen, and Robert Madsen, and Günther H Peters
Department of Chemistry, Technical University of Denmark, Kgs. Lyngby, Denmark.

We studied secretory phospholipase A(2) type IIA (sPLA(2)) activity toward phospholipids that are derivatized in the sn-1 position of the glycerol backbone. We explored what type of side group (small versus bulky groups, hydrophobic versus polar groups) can be introduced at the sn-1 position of the glycerol backbone of glycerophospholipids and at the same time be hydrolyzed by sPLA(2). The biophysical characterization revealed that the modified phospholipids can form multilamellar vesicles, and several of the synthesized sn-1 functionalized phospholipids were hydrolyzed by sPLA(2). Molecular dynamics simulations provided detailed insight on an atomic level that can explain the observed sPLA(2) activity toward the different phospholipid analogs. The simulations revealed that, depending on the nature of the side chain located at the sn-1 position, the group may interfere with an incoming water molecule that acts as the nucleophile in the enzymatic reaction. The simulation results are in agreement with the experimentally observed sPLA(2) activity toward the different phospholipid analogs.

UI MeSH Term Description Entries
D008081 Liposomes Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. Niosomes,Transferosomes,Ultradeformable Liposomes,Liposomes, Ultra-deformable,Liposome,Liposome, Ultra-deformable,Liposome, Ultradeformable,Liposomes, Ultra deformable,Liposomes, Ultradeformable,Niosome,Transferosome,Ultra-deformable Liposome,Ultra-deformable Liposomes,Ultradeformable Liposome
D008956 Models, Chemical Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Chemical Models,Chemical Model,Model, Chemical
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D010743 Phospholipids Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. Phosphatides,Phospholipid
D003198 Computer Simulation Computer-based representation of physical systems and phenomena such as chemical processes. Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014867 Water A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Hydrogen Oxide
D054497 Phospholipases A2, Secretory A subcategory of phospholipases A2 that are secreted from cells. They are 14 kDa proteins containing multiple disulfide-bonds and access their substrate via an interfacial binding site that interacts with phospholipid membranes. In addition specific PHOSPHOLIPASE A2 RECEPTORS can bind to and internalize the enzymes. Secreted Phospholipase A2,sPLA2,Phospholipases A2, Secreted,SPLA2 Phospholipases,Secreted Phospholipases A2,Secretory Phospholipase A2,sPLA(2),sPLA2s,A2, Secreted Phospholipase,Phospholipase A2, Secreted,Phospholipase A2, Secretory,Phospholipases, SPLA2,Secretory Phospholipases A2

Related Publications

Lars Linderoth, and Thomas L Andresen, and Kent Jørgensen, and Robert Madsen, and Günther H Peters
Each phospholipase A2 type exhibits distinct selectivity toward sn-1 ester, alkyl ether, and vinyl ether phospholipids.
January 2022, Biochimica et biophysica acta. Molecular and cell biology of lipids,
Lars Linderoth, and Thomas L Andresen, and Kent Jørgensen, and Robert Madsen, and Günther H Peters
Selectivity of cytosolic phospholipase A2 type IV toward arachidonyl phospholipids.
July 2015, Journal of molecular recognition : JMR,
Lars Linderoth, and Thomas L Andresen, and Kent Jørgensen, and Robert Madsen, and Günther H Peters
Hydrolytic activities of human pancreatic phospholipase A2 and endotoxin-stimulated endogenous phospholipase A2 toward membrane phospholipids of erythrocytes.
March 1985, The Journal of surgical research,
Lars Linderoth, and Thomas L Andresen, and Kent Jørgensen, and Robert Madsen, and Günther H Peters
Halogenated phospholipids regulate secretory phospholipase A2 group IIA activity.
January 2013, Chemistry and physics of lipids,
Lars Linderoth, and Thomas L Andresen, and Kent Jørgensen, and Robert Madsen, and Günther H Peters
Mechanism of phospholipase A2 action toward mixed micelles of detergent and phospholipids.
January 1978, Advances in experimental medicine and biology,
Lars Linderoth, and Thomas L Andresen, and Kent Jørgensen, and Robert Madsen, and Günther H Peters
[Phospholipase A2 and reacylation of phospholipids].
July 1987, Biokhimiia (Moscow, Russia),
Lars Linderoth, and Thomas L Andresen, and Kent Jørgensen, and Robert Madsen, and Günther H Peters
Molecular basis of phospholipase A2 inhibition by petrosaspongiolide M.
July 2002, Chembiochem : a European journal of chemical biology,
Lars Linderoth, and Thomas L Andresen, and Kent Jørgensen, and Robert Madsen, and Günther H Peters
Phospholipase from Trypanosoma brucei releases arachidonic acid by sequential sn-1, sn-2 deacylation of phospholipids.
April 2001, Molecular and biochemical parasitology,
Lars Linderoth, and Thomas L Andresen, and Kent Jørgensen, and Robert Madsen, and Günther H Peters
Lipid peroxidation and phospholipase A2 activity in liposomes composed of unsaturated phospholipids: a structural basis for enzyme activation.
August 1988, Biochimica et biophysica acta,
Lars Linderoth, and Thomas L Andresen, and Kent Jørgensen, and Robert Madsen, and Günther H Peters
Hydrolysis of 1-palmitoyl-2-[6-(pyren-1-yl)]hexanoyl-sn-glycero- 3-phospholipids by phospholipase A2: effect of the polar head-group.
February 1987, Biochimica et biophysica acta,
Copied contents to your clipboard!