title: NMR structures of phospholipase A2 reveal conformational changes during interfacial activation.
abstract: It has long been proposed that the higher activity of phospholipase A2 (PLA2) for substrates presented as multimolecular aggregates compared to dispersed molecules (interfacial activation) arises due to a conformational change in the enzyme. X-ray studies have, however, failed to identify any such change. Here we report the solution structures of porcine pancreatic PLA2 both free and as a ternary complex with micelles and a competitive inhibitor. Important differences between these structures indicate that conformational changes may play an important role in the mechanism of interfacial activation in PLA2s.
authors.affiliation: Department of Enzymology and Protein Engineering, Utrecht University, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: van den Berg
authors.forename: M
authors.initials: M
authors.lastname: Tessari
authors.forename: R
authors.initials: R
authors.lastname: Boelens
authors.forename: R
authors.initials: R
authors.lastname: Dijkman
authors.forename: G H
authors.initials: GH
authors.lastname: de Haas
authors.forename: R
authors.initials: R
authors.lastname: Kaptein
authors.forename: H M
authors.initials: HM
authors.lastname: Verheij
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D004789:Enzyme Activation; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013552:Swine; D014867:Water / Q000737:chemistry
chemical_list: C095491:1-thio-octyl-2-heptylphosphonyl-1-deoxyglycero-3-phosphoglycol; D008055:Lipids; D008823:Micelles; D010743:Phospholipids; D014867:Water; D010767:Phosphorylcholine; C028810:dodecylphosphocholine; D010741:Phospholipases A; D054467:Phospholipases A2