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Neurotransmitter:sodium symporters (NSS) serve as targets for drugs including antidepressants and psychostimulants. Here authors report the X-ray structure of the prokaryotic NSS member, LeuT, in

We used crystallographic and functional studies on the leucine transporter (LeuT), a model for neurotransmitter sodium symporters, to show that various amino acid substrates induce the same occluded conformational state and that a competitive inhibitor, tryptophan (Trp), traps LeuT in an open-to-out conformation.

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TM helices equivalent to TM1 in LeuT (henceforth TM1’) show a centrally-located discontinuous region in all LeuT-fold transporters crystallized so far. The structure of TM6’ is discontinuous in LeuT and most LeuT-fold members, though TM6’ is bent in CaiT [11,14] and fully continuous in BetP .

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The x-ray structure of LeuT, a bacterial homologue of Na + /Cl −-dependent neurotransmitter transporters, provides a great opportunity to better understand the molecular basis of monovalent cation selectivity in ion-coupled transporters.LeuT possesses two ion binding sites, NA1 and NA2, which are highly selective for Na +.Extensive all-atom free-energy molecular dynamics simulations of LeuT

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May 10, 2009 · Following membrane solubilization in 1% (w/v) n-dodecyl-β-D-maltoside, we purified LeuT using Ni 2+-affinity chromatography for binding and transport activity studies. (24 February 2009). 21.

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Similarly, in co-crystal structures of LeuT with three SSRIs (sertraline, R-fluoxetine, and S-fluoxetine), the drug molecules all bind to LeuT at the S2 site and in a very similar manner (Figure 2 and Table 1).The SSRI binding site shares a number of residues with the S1 substrate binding site.

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Alternating access mechanisms of LeuT-fold transporters: trailblazing towards the promised energy landscapes. and outward-facing (OF, right) conformations of LeuT (PDB 3TT3 and 3TT1), Mhp1 (PDB 2 × 79 and 2JLN), and BetP (PDB 4LLH chain c and b) are shown. Scaffold helices 3, 4, 8, and 9 are shown as a grey surface within the outline of

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Under these conditions, the K d for leucine binding to wild-type LeuT (LeuT WT) is 31.7±0.9 nM and to the F253A mutant is 99.4±5.1 nM (supplementary Fig S1 online, supplementary Table I online), values similar to those previously reported by the Javitch and Gouaux groups [14, 17, 18].

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Dec 12, 2008 · All cocrystals diffracted to 1.8–2.3 Å resolution and the resulting structures refined well . The structures of LeuT in complex with each of the substrates (glycine, alanine, leucine, methionine, 4-F-Phe) are similar, with overall Cα RMSDs ranging from 0.2 to 0.3 Å (Fig. 1C) despite the 132 Å 3 variation in substrate volume.

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LeuT F253A–Leu (8–10 mg ml −1) in the presence of 7% (wt/vol) DMPC‐CHAPSO bicelles was crystallized by vapour diffusion at 20 °C with the crystallization reservoir solution containing 100 mM sodium acetate (pH 4.7), 29% (vol/vol) MPD (2‐methyl‐2,4 pentanediol) and 10% (vol/vol) PEG400 and 50 mM MgCl 2. LeuT F253A–SeMet crystals

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Substrate binds in the S1 site of the F253A mutant of LeuT, a neurotransmitter sodium symporter homologue Hui Wang 1 &EricGouaux1,2+ 1Vollum Institute, and 2Howard Hughes Medical Institute, Oregon Health & Science University, Portland, Oregon, USA LeuT serves as the model protein for understanding the relation-

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In a recent computational investigation of LeuT/DDM proteomicelles,24 we found that at high DDM ratios the S2 site could be occluded by nontransient insertion of DDM, which Figure 1. Schematic representation of the conditions for the all-atom MD simulations of LeuT/lipid/detergent complexes (protein:detergent:lipid

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The crystal structure of LeuT, a bacterial member of this family, provided the first atomic-level glimpse into overall cific,24 saturable25 and susceptible to inhibition by cocaine21 and

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Dec 12, 2008 · TM11 also undergoes a substantial displacement in the LeuT-Trp complex. Concomitant with the outward rotation of neighboring TM6a, TM11 shifts inward by ∼2 Å in the region around W467, whereas the indole side chain of W467 on the interior face of the helix rotates 90° relative to its position in the occluded-state structures.

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In addition to the three dimer systems (WT, MUT, and ALA), a model of monomeric, inward-facing LeuT interacting with the Fab fragment was also constructed (FAB), based on the PDB: 3TT3 crystal structure.In the light chain of Fab, disulfide bonds were added between Cys-23 and Cys-92 as well as between Cys-138 and Cys-198.

Mar 21, 2020 · Paul O’Dette – Rippe: Works for lute ‘Un perfaict sonneur de Leut’ (2019) [24bit FLAC]

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Simulations were performed for LeuT dimer, given that NSS members usually exist as dimers or oligomers (28 – 32). Each dimer was embedded in a 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) membrane bilayer with dimensions of 155 × 110 Å 2 and a solution with 150 m m NaCl.

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bound water molecule. Another water molecule, located in the same position between Arg30 and Asp404 as one observed in the drug-free structure of LeuT 16, mediates the two residues’ interactions

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Oct 20, 2019 · A backformed singular Leut m (“ person ”) may be heard in colloquial speech. It is rare and usually humorous. It is rare and usually humorous. Further reading [ edit ]

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ture of LeuT in a fully outward-open conformation with tryptophan bound was published (23) and in 2012, the first inward-open LeuT structure was published (24). Compari-son of the outward- and inward-facing crystal structures in-dicates that the conformational change connecting these structures can be largely described as a movement of a

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Als Aushilfe steht sie ihrem Sohn bei, in einem Bekleidungsgeschäft in der Lugner City: Munni Mundolia aus Indien. Wie sich ihre Kundschaft in Wien verändert hat, und was sie gegen Ladendiebstahl unternimmt, erzählt sie Christoph Schütz in der aktuellen Ausgabe von Leut’ in Wien.

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INTERMEDIATE SCHOOLREACH PACK #24 Page 2 of 7. 27. What relative of the camel lives in South America? A. LLAMA (Accept VICUNA, ALPACA or GUANACO) 40-POINTSNAPPERS TO END THE ROUND 28. Using the Mohs Scale of Hardness, which substance is considered hardest? A. DIAMOND 29. What is the third sign of the zodiac, symbolized by twins?

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