title: Molecular dynamics simulation of a phospholipase A2-substrate complex.
abstract: We have used knowledge of the three-dimensional structure of phospholipids and phospholipases A2 together with biochemical data, computer graphics modelling and a 48 ps molecular dynamics simulation to predict the structure of a phospholipase A2-substrate complex. There is remarkable similarity between this predicted structure of enzyme-substrate complex and the structure that can be deduced from the observed enzyme-inhibitor complex. Molecular dynamics simulation highlights the importance of the calcium-ion in substrate binding and the persistence of the His-48 to water-hydrogen bond is compatible with the proposed role of this water molecule as the nucleophile in catalysis.
authors.affiliation: Protein Engineering Department, AFRC Institute of Food Research, Reading, UK.
authors.forename: S T
authors.initials: ST
authors.lastname: Jones
authors.forename: P
authors.initials: P
authors.lastname: Ahlström
authors.forename: H J
authors.initials: HJ
authors.lastname: Berendsen
authors.forename: R W
authors.initials: RW
authors.lastname: Pickersgill
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium; D003198:Computer Simulation; D008958:Models, Molecular; D015394:Molecular Structure; D010713:Phosphatidylcholines / Q000737:chemistry*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D054467:Phospholipases A2; D013379:Substrate Specificity; D013552:Swine; D014867:Water
chemical_list: D010713:Phosphatidylcholines; D014867:Water; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium