Affinity and path of binding xylopyranose unto E. coli xylose permease

作者：Wambo Thierry O; Chen Liao Y; Phelix Clyde; Perry George

来源：Biochemical and Biophysical Research Communications, 2017, 494(1-2): 202-206.

DOI：10.1016/j.bbrc.2017.10.053

• E. coli xylose permease
• Glucose transporter
• Transmembrane protein
• Binding affinity
• Free energy
• Molecular dynamics

Glucose transporters (GLUTs), expressed in all types of human cells, are responsible for the uptake of sugars as the primary energy source for the normal functions of good cells and for the abnormal growth of cancer cells. The E. coli xylose permease (XylE), a homologue of human GLUTs, has been investigated more thoroughly than other major facilitator proteins in the current literature. In this paper, we present a molecular dynamics (MD) study of an all-atom model system to elucidate the atomistic details and the free-energy landscape along the path of binding a xylopyranose (XYP) from the extracellular space to the inside of the transporter protein XylE. From the MD simulations, the Gibbs free energy of binding was found to be -4.4 kcal/mol in agreement with the experimental value of 4.7 kcal/mol. The accuracy of our study is further shown in the computed hydration energy of XYP of 14.6 kcal/mol in comparison with the experimental data of 15.0 kcal/mol. Along the binding path, the Gibbs free energy of the XYPXyIE complex first rises from zero in the dissociated state to approximately 4 kcal/mol in the transition state (when XyIE slightly increases its opening toward the extracellular side to accommodate XYP) before dropping down to -9.0 kcal/mol in the bound state. These quantitative insights indicate the fast equilibration between the bound and the unbound states of XylE and XYP. They also serve as an atomistic-dynamic corroboration of the experimental conclusion that XylE is a high-affinity sugar transporter.

• 出版日期2017-12-9