Protein Science, Vol 7, Issue 6 1359-1367, Copyright © 1998 by Cold Spring Harbor Laboratory Press

ARTICLE

Conformational change in the activation of lipase: An analysis in terms of low-frequency normal modes

S. JAASKELAINEN, C. S. VERMA, R. E. HUBBARD, P. LINKO and LSD. CAVES
Protein Structure Research Group, Department of Chemistry, University of York, Heslington, York YO1 5DD, United Kingdom Laboratory of Bioprocess Engineering, Helsinki University of Technology, P.O. Box 6100, 02015 HUT, Finland

The interfacial activation of Rhizomucor miehei lipase (RmL) involves the motion of an {alpha}-helical region (residues 82-96) which acts as a ``lid'' over the active site of the enzyme, undergoing a displacement from a ``closed'' to an ``open'' conformation upon binding of substrate. Normal mode analyses performed in both low and high dielectric media reveal that low-frequency vibrational modes contribute significantly to the conformational transition between the closed and open conformations. In these modes, the lid displacement is coupled to local motions of active site loops as well as global breathing motions. Atomic fluctuations of the first hinge of the lid (residues 83-84) are substantially larger in the low dielectric medium than in the high dielectric medium. Our results also suggest that electrostatic interactions of Arg86 play an important role in terms of both the intrinsic stability of the lid and its displacement, through enhancement of hinge mobility in a high dielectric medium. Additional calculations demonstrate that the observed patterns of atomic fluctuations are an intrinsic feature of the protein structure and not dependent on the nature of specific energy minima.
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