@article {46670,
	title = {Molecular dynamics simulations of the human glucose transporter GLUT1.},
	journal = {PLoS One},
	volume = {10},
	year = {2015},
	month = {2015 Apr 28},
	pages = {e0125361},
	abstract = {<p>Glucose transporters (GLUTs) provide a pathway for glucose transport across membranes. Human GLUTs are implicated in devastating diseases such as heart disease, hyper- and hypo-glycemia, type 2 diabetes and caner. The human GLUT1 has been recently crystalized in the inward-facing open conformation. However, there is no other structural information for other conformations. The X-ray structures of E. coli Xylose permease (XylE), a glucose transporter homolog, are available in multiple conformations with and without the substrates D-xylose and D-glucose. XylE has high sequence homology to human GLUT1 and key residues in the sugar-binding pocket are conserved. Here we construct a homology model for human GLUT1 based on the available XylE crystal structure in the partially occluded outward-facing conformation. A long unbiased all atom molecular dynamics simulation starting from the model can capture a new fully opened outward-facing conformation. Our investigation of molecular interactions at the interface between the transmembrane (TM) domains and the intracellular helices (ICH) domain in the outward- and inward-facing conformation supports that the ICH domain likely stabilizes the outward-facing conformation in GLUT1. Furthermore, inducing a conformational transition, our simulations manifest a global asymmetric rocker switch motion and detailed molecular interactions between the substrate and residues through the water-filled selective pore along a pathway from the extracellular to the intracellular side. The results presented here are consistent with previously published biochemical, mutagenesis and functional studies. Together, this study shed light on the structure and functional relationships of GLUT1 in multiple conformational states.</p>
},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0125361},
	author = {Park, Min-Sun}
}
@article {45904,
	title = {Proton-coupled sugar transport in the prototypical major facilitator superfamily protein XylE.},
	journal = {Nature Communication},
	volume = {5},
	year = {2014},
	month = {2014 - Aug},
	pages = {4521},
	abstract = {<p>The major facilitator superfamily (MFS) is the largest collection of structurally related membrane proteins that transport a wide array of substrates. The proton-coupled sugar transporter XylE is the first member of the MFS that has been structurally characterized in multiple transporting conformations, including both the outward and inward-facing states. Here we report the crystal structure of XylE in a new inward-facing open conformation, allowing us to visualize the rocker-switch movement of the N-domain against the C-domain during the transport cycle. Using molecular dynamics simulation, and functional transport assays, we describe the movement of XylE that facilitates sugar translocation across a lipid membrane and identify the likely candidate proton-coupling residues as the conserved Asp27 and Arg133. This study addresses the structural basis for proton-coupled substrate transport and release mechanism for the sugar porter family of proteins.</p>
},
	issn = {2041-1723},
	doi = {10.1038/ncomms5521},
	author = {Wisedchaisri, Goragot and Park, Min-Sun and Iadanza, Matthew G and Zheng, Hongjin and Gonen, Tamir}
}
