Title of article :
A Molecular Dynamics Investigation of Mono and Dimeric States of the Outer Membrane Enzyme OMPLA
Author/Authors :
Marc Baaden، نويسنده , , Christoph Meier، نويسنده , , Mark S.P. Sansom، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2003
Pages :
13
From page :
177
To page :
189
Abstract :
OMPLA is a phospholipase found in the outer membranes of many Gram-negative bacteria. Enzyme activation requires calcium-induced dimerisation plus bilayer perturbation. As the conformation of OMPLA in the different crystal forms (monomer versus dimer; with/without bound Ca2+) is remarkably similar we have used multi-nanosecond molecular dynamics (MD) simulations to probe possible differences in conformational dynamics that may be related to enzyme activation. Simulations of calcium-free monomeric OMPLA, of the Ca2+-bound dimer, and of the Ca2+-bound dimer with a substrate analogue covalently linked to the active site serine have been performed, all with the protein embedded in a phospholipid (POPC) bilayer. All simulations were stable, but differences in the dynamic behaviour of the protein between the various states were observed. In particular, the stability of the active site and the hydrophobic substrate-binding cleft varied. Dimeric OMPLA is less flexible than monomeric OMPLA, especially around the active site. In the absence of bound substrate analogue, the hydrophobic substrate-binding cleft of dimeric OMPLA collapses. A model is proposed whereby the increased stability of the active site in dimeric OMPLA is a consequence of the local ordering of water around the nearby calcium ion. The observed collapse of the substrate-binding cleft may explain the experimentally observed occurrence of multiple dimer conformations of OMPLA, one of which is fully active while the other shows significantly reduced activity.
Keywords :
Ca2+ , OMPLA , membrane protein , Molecular dynamics , substrate-binding cleft
Journal title :
Journal of Molecular Biology
Serial Year :
2003
Journal title :
Journal of Molecular Biology
Record number :
1242913
Link To Document :
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