title: Selectivity of cytosolic phospholipase A2 type IV toward arachidonyl phospholipids.
abstract: Cytosolic phospholipase A2 (cPLA2 ) is an interesting protein involved in inflammatory processes and various diseases. Its catalytic mechanism as well as its substrate specificity for arachidonyl phospholipids is not typical for other phospolipases. Furthermore, a lid structure, which ensures a hydrophilic surface of the protein without any substrate bound and the movement of this flexible loop to make the hydrophobic active site accessible, is of high interest. Therefore, the focus of this work was to determine the binding mode of cPLA2 with various substrates, such as arachidonic acid, a synthetic inhibitor, a saturated phospholipid, and most importantly an arachidonyl phospholipid. To understand the selectivity of the protein toward the arachidonyl phospholipid and the interaction in a protein-ligand complex, molecular dynamics simulations were performed using the GROMOS suite of simulation programs. The simulations provide insight into the protein and showed that selective binding of arachidonyl phospholipids is because of the shape of the sn-2 tail. The amino acids Asn555 and Ala578 are involved in the strongest interactions observed in the protein-ligand complexes.
authors.affiliation: Department of Material Sciences and Process Engineering, Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, 1190, Vienna, Austria.
authors.forename: Melanie
authors.initials: M
authors.lastname: Grandits
authors.affiliation: Department of Material Sciences and Process Engineering, Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, 1190, Vienna, Austria.
authors.forename: Chris
authors.initials: C
authors.lastname: Oostenbrink
mesh_terms: D000409:Alanine / Q000737:chemistry; D016718:Arachidonic Acid / Q000737:chemistry; D001216:Asparagine / Q000737:chemistry; D001665:Binding Sites; D003593:Cytoplasm / Q000378:metabolism; D054513:Group IV Phospholipases A2 / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010743:Phospholipids / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D010743:Phospholipids; D016718:Arachidonic Acid; D001216:Asparagine; D054513:Group IV Phospholipases A2; D000409:Alanine
keywords: GROMOS; arachidonic acid; arachidonyl phospholipid; cytosolic phospholipase A2 type IV; molecular dynamics simulations; α/β hydrolase