Tetrameric mouse acetylcholinesterase: continuum diffusion rate calculations
by solving the steady-state Smoluchowski equation using finite element
methods.
The tetramer is the most important form for acetylcholinesterase in
physiological conditions, i.e., in the neuromuscular junction and
the nervous system. It is important to study the diffusion of acetylcholine
to the active sites of the tetrameric enzyme to understand the overall
signal transduction process in these cellular components. Crystallographic
studies revealed two different forms of tetramers, suggesting a flexible
tetramer model for acetylcholinesterase. Using a recently developed
finite element solver for the steady-state Smoluchowski equation,
we have calculated the reaction rate for three mouse acetylcholinesterase
tetramers using these two crystal structures and an intermediate
structure as templates. Our results show that the reaction rates
differ for different individual active sites in the compact tetramer
crystal structure, and the rates are similar for different individual
active sites in the other crystal structure and the intermediate
structure. In the limit of zero salt, the reaction rates per active
site for the tetramers are the same as that for the monomer, whereas
at higher ionic strength, the rates per active site for the tetramers
are approximately 67\%-75\% of the rate for the monomer. By analyzing
the effect of electrostatic forces on ACh diffusion, we find that
electrostatic forces play an even more important role for the tetramers
than for the monomer. This study also shows that the finite element
solver is well suited for solving the diffusion problem within complicated
geometries.
%0 Journal Article
%1 Zhan_2005_1659
%A Zhang, Deqiang
%A Suen, Jason
%A Zhang, Yongjie
%A Song, Yuhua
%A Radic, Zoran
%A Taylor, Palmer
%A Holst, Michael J
%A Bajaj, Chandrajit
%A Baker, Nathan A
%A McCammon, J. Andrew
%D 2005
%J Biophys. J.
%K , 15626705 Acetylcholine, Acetylcholinesterase, Anal, Animals, Binding Binding, Chemical, Complexes, Computer Conformation, Crystallization, Crystallography, Diffusion, Element Finite Gov't, Kinetics, Mice, Models, Molecular, Multiprotein Non-P.H.S., Non-U.S. Protein Research Simulation, Sites, Support, U.S. ysis,
%N 3
%P 1659--1665
%R 10.1529/biophysj.104.053850
%T Tetrameric mouse acetylcholinesterase: continuum diffusion rate calculations
by solving the steady-state Smoluchowski equation using finite element
methods.
%U http://dx.doi.org/10.1529/biophysj.104.053850
%V 88
%X The tetramer is the most important form for acetylcholinesterase in
physiological conditions, i.e., in the neuromuscular junction and
the nervous system. It is important to study the diffusion of acetylcholine
to the active sites of the tetrameric enzyme to understand the overall
signal transduction process in these cellular components. Crystallographic
studies revealed two different forms of tetramers, suggesting a flexible
tetramer model for acetylcholinesterase. Using a recently developed
finite element solver for the steady-state Smoluchowski equation,
we have calculated the reaction rate for three mouse acetylcholinesterase
tetramers using these two crystal structures and an intermediate
structure as templates. Our results show that the reaction rates
differ for different individual active sites in the compact tetramer
crystal structure, and the rates are similar for different individual
active sites in the other crystal structure and the intermediate
structure. In the limit of zero salt, the reaction rates per active
site for the tetramers are the same as that for the monomer, whereas
at higher ionic strength, the rates per active site for the tetramers
are approximately 67\%-75\% of the rate for the monomer. By analyzing
the effect of electrostatic forces on ACh diffusion, we find that
electrostatic forces play an even more important role for the tetramers
than for the monomer. This study also shows that the finite element
solver is well suited for solving the diffusion problem within complicated
geometries.
@article{Zhan_2005_1659,
abstract = {The tetramer is the most important form for acetylcholinesterase in
physiological conditions, i.e., in the neuromuscular junction and
the nervous system. It is important to study the diffusion of acetylcholine
to the active sites of the tetrameric enzyme to understand the overall
signal transduction process in these cellular components. Crystallographic
studies revealed two different forms of tetramers, suggesting a flexible
tetramer model for acetylcholinesterase. Using a recently developed
finite element solver for the steady-state Smoluchowski equation,
we have calculated the reaction rate for three mouse acetylcholinesterase
tetramers using these two crystal structures and an intermediate
structure as templates. Our results show that the reaction rates
differ for different individual active sites in the compact tetramer
crystal structure, and the rates are similar for different individual
active sites in the other crystal structure and the intermediate
structure. In the limit of zero salt, the reaction rates per active
site for the tetramers are the same as that for the monomer, whereas
at higher ionic strength, the rates per active site for the tetramers
are approximately 67\%-75\% of the rate for the monomer. By analyzing
the effect of electrostatic forces on ACh diffusion, we find that
electrostatic forces play an even more important role for the tetramers
than for the monomer. This study also shows that the finite element
solver is well suited for solving the diffusion problem within complicated
geometries.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Zhang, Deqiang and Suen, Jason and Zhang, Yongjie and Song, Yuhua and Radic, Zoran and Taylor, Palmer and Holst, Michael J and Bajaj, Chandrajit and Baker, Nathan A and McCammon, J. Andrew},
biburl = {https://www.bibsonomy.org/bibtex/230a48252cacdf64dfa7d8d34a55f4819/hake},
description = {The whole bibliography file I use.},
doi = {10.1529/biophysj.104.053850},
file = {Zhan_2005_1659.pdf:Zhan_2005_1659.pdf:PDF},
interhash = {7f6a379086aa35337255e4929e7f9651},
intrahash = {30a48252cacdf64dfa7d8d34a55f4819},
journal = {Biophys. J.},
keywords = {, 15626705 Acetylcholine, Acetylcholinesterase, Anal, Animals, Binding Binding, Chemical, Complexes, Computer Conformation, Crystallization, Crystallography, Diffusion, Element Finite Gov't, Kinetics, Mice, Models, Molecular, Multiprotein Non-P.H.S., Non-U.S. Protein Research Simulation, Sites, Support, U.S. ysis,},
month = Mar,
number = 3,
pages = {1659--1665},
pii = {biophysj.104.053850},
pmid = {15626705},
timestamp = {2009-06-03T11:21:39.000+0200},
title = {Tetrameric mouse acetylcholinesterase: continuum diffusion rate calculations
by solving the steady-state Smoluchowski equation using finite element
methods.},
url = {http://dx.doi.org/10.1529/biophysj.104.053850},
volume = 88,
year = 2005
}