THE LIPASE COLIPASE COMPLEX IS ACTIVATED BY A MICELLE - NEUTRON CRYSTALLOGRAPHIC EVIDENCE/

The catalytic activity of most lipases depends on the aggregation stat e of their substrates. It is supposed that lipase activation requires the unmasking and structuring of the enzyme's active site through conf ormational changes involving the presence of oil-in-water droplets. Th is phenomenon has been called interfacial activation. Here, we report the crystal structure of the pancreatic activated lipase/colipase/mice lle complex as determined using the D2O/H2O contrast variation low res olution neutron diffraction method. We find that a disk-shaped micelle interacts extensively with the concave face of colipase (CL) and the distal tip of the C-terminal domain of lipase away from the active sit e of the enzyme. Such interaction appears to help stabilizing the lipa se-CL interaction. Consequently, we conclude that lipase activation is not interfacial but occurs in the aqueous phase and it is mediated by CL and a micelle. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved.