期刊
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
卷 79, 期 10, 页码 2813-2827出版社
WILEY
DOI: 10.1002/prot.23107
关键词
lactate dehydrogenase; glyceraldehyde-3-phosphate dehydrogenasc; fructose-1,6-bisphosphate aldolase; triosphosphate isomerase; Poisson-Boltzmann
资金
- NIH [P20 RR016741]
- NIH/NIGMS [2 R15 GM055929-03]
- University of North Dakota Computational Chemistry and Biology Network
- UNCF/MERCK
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-Factin interactions in creating initial complexes critical for compartmentation.
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