NMR structures of phospholipase A2 reveal conformational changes during interfacial activation.
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.
van den Berg
B
B
Department of Enzymology and Protein Engineering, Utrecht University, The Netherlands.
Tessari
M
M
Boelens
R
R
Dijkman
R
R
de Haas
G H
GH
Kaptein
R
R
Verheij
H M
HM
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
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