title: Molecular dynamics simulations of Na(+) and leucine transport by LeuT.
abstract: Molecular dynamics simulations are used to gain insight into the binding of Na(+) and leucine substrate to the bacterial amino acid transporter LeuT, focusing on the crystal structures of LeuT in the outward-open and inward-open states. For both conformations of LeuT, a third Na(+) binding site involving Glu290 in addition to the two sites identified from the crystal structures is observed. Once the negative charge from Glu290 in the inward-open LeuT is removed, the ion bound to the third site is ejected from LeuT rapidly, suggesting that the protonation state of Glu290 regulates Na(+) binding and release. In Cl(-)-dependent transporters where Glu290 is replaced by a neutral serine, a Cl(-) ion would be required to replace the role of Glu290. Thus, the simulations provide insights into understanding Na(+) and substrate transport as well as Cl(-)-independence of LeuT.
authors.affiliation: Research School of Biology, Australian National University, Canberra, ACT 2601, Australia. Electronic address: rong.chen@anu.edu.au.
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Research School of Biology, Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Shin-Ho
authors.initials: SH
authors.lastname: Chung
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D018698:Glutamic Acid / Q000737:chemistry*; D017136:Ion Transport; D007700:Kinetics; D007930:Leucine / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D050479:Neurotransmitter Transport Proteins / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011522:Protons; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D050479:Neurotransmitter Transport Proteins; D011522:Protons; D018698:Glutamic Acid; D012964:Sodium; D007930:Leucine
keywords: Ion transport; LeuT; Leucine transporter; Molecular dynamics; Substrate binding