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Conformational change in the activation of lipase: An analysis in terms of low‐frequency normal modes
Author(s) -
Jääskeläinen Sanna,
Verma Chandra S.,
Hubbard Roderick E.,
Lestko Pekka,
Caves Leo S.D.
Publication year - 1998
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560070612
Subject(s) - rhizomucor miehei , hinge , lipase , displacement (psychology) , chemistry , dielectric , chemical physics , normal mode , active site , maxima and minima , molecular physics , crystallography , materials science , physics , vibration , classical mechanics , enzyme , optoelectronics , triacylglycerol lipase , organic chemistry , psychology , mathematical analysis , mathematics , psychotherapist , quantum mechanics
The interfacial activation of Rhizomucor miehei lipase (RmL) involves the motion of an α‐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.