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Ionic strength dependence of F‐actin and glycolytic enzyme associations: A Brownian dynamics simulations approach
Author(s) -
Forlemu Neville Y.,
Njabon Eric N.,
Carlson Kristine L.,
Schmidt Elizabeth S.,
Waingeh Victor F.,
Thomasson Kathryn A.
Publication year - 2011
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.23107
Subject(s) - aldolase a , glyceraldehyde 3 phosphate dehydrogenase , fructose bisphosphate aldolase , ionic strength , brownian dynamics , glycolysis , enzyme , dehydrogenase , actin , dhap , triosephosphate isomerase , chemistry , biophysics , biochemistry , lactate dehydrogenase , phosphofructokinase 1 , biology , phosphofructokinase , brownian motion , physics , quantum mechanics , aqueous solution
The association of glycolytic enzymes with F‐actin is proposed to be one mechanism by which these enzymes are compartmentalized, and, as a result, may possibly play important roles for: regulation of the glycolytic pathway, potential substrate channeling, and increasing glycolytic flux. Historically, in vitro experiments have shown that many enzyme/actin interactions are dependent on ionic strength. Herein, Brownian dynamics (BD) examines how ionic strength impacts the energetics of the association of F‐actin with the glycolytic enzymes: lactate dehydrogenase (LDH), glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), fructose‐1,6‐bisphosphate aldolase (aldolase), and triose phosphate isomerase (TPI). The BD simulations are steered by electrostatics calculated by Poisson‐Boltzmann theory. The BD results confirm experimental observations that the degree of association diminishes as ionic strength increases but also suggest that these interactions are significant, at physiological ionic strengths. Furthermore, BD agrees with experiments that muscle LDH, aldolase, and GAPDH interact significantly with F‐actin whereas TPI does not. BD indicates similarities in binding regions for aldolase and LDH among the different species investigated. Furthermore, the residues responsible for salt bridge formation in stable complexes persist as ionic strength increases. This suggests the importance of the residues determined for these binary complexes and specificity of the interactions. That these interactions are conserved across species, and there appears to be a general trend among the enzymes, support the importance of these enzyme‐F‐actin interactions in creating initial complexes critical for compartmentation. Proteins 2011; © 2011 Wiley‐Liss, Inc.