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2.A.22.4.2
The amino acid (leucine):2 Na+ symporter, LeuTAa (Yamashita et al., 2005). LeuT possesses two ion binding sites, NA1 and NA2, both highly specific for Na+ but with differing mechanisms of binding (Noskov and Roux, 2008). X-ray structures have been determined for LeuT in substrate-free outward-open and apo inward-open states (Krishnamurthy and Gouaux, 2012).  Extracytoplasmic substrate binding at an allosteric site controls activity (Zhao et al. 2011).  It has been proposed that the 5 TMS repeat derived from a DedA domain (9.B.27; Khafizov et al. 2010).  Mechanistic aspect of Na+ binding have been studied (Perez and Ziegler 2013).  Structural studies of mutant LeuT proteins suggest how antidepressants bind to biogenic amine transporters (Wang et al. 2013).  The detailed mechanism was studied by Zhao and Noskov, 2013.  Uptake involves movement of the substrate amino acid from the outward facing binding site, S1, to the inward facing binding site, S2, coupled with confrmational changes in the protein (Cheng and Bahar 2013).  The complete substrate translocation pathway has been proposed (Cheng and Bahar 2014). The inward facing conformation of LeuT has been solved (Grouleff et al. 2015).  Substrate-induced unlocking of the inner gatemay determinethe catalytic efficiency of the transporter (Billesbølle et al. 2015). Of the two Na+ binding sites, occupation of Na2 stabilizes outward-facing conformations presumably through a direct interaction between Na+ and transmembrane helices 1 and 8 whereas Na+ binding at Na1 influences conformational change through a network of intermediary interactions (Tavoulari et al. 2015). TMS1A movements revealed a substantially different inward-open conformation in lipid bilayer from that inferred from the crystal structure, especiallly with respect to the inner vestibule (Sohail et al. 2016).

Accession Number:O67854
Protein Name:LeuTAa
Length:513
Molecular Weight:57408.00
Species:Aquifex aeolicus [63363]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Leucine, Na+

Cross database links:

HEGENOM: HBG702834
RefSeq: NP_214423.1   
Entrez Gene ID: 1193843   
Pfam: PF00209   
Drugbank: Drugbank Link   
BioCyc: AAEO224324:AQ_2077-MONOMER   
KEGG: aae:aq_2077   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005328 F:neurotransmitter:sodium symporter activity
GO:0006836 P:neurotransmitter transport

References (1)

[1] “The complete genome of the hyperthermophilic bacterium Aquifex aeolicus.”  Deckert G.et.al.   9537320
Structure:
2A65   2Q6H   2Q72   2QB4   2QEI   2QJU   3F3A   3F3C   3F3D   3F3E   [...more]

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MEVKREHWAT RLGLILAMAG NAVGLGNFLR FPVQAAENGG GAFMIPYIIA FLLVGIPLMW 
61:	IEWAMGRYGG AQGHGTTPAI FYLLWRNRFA KILGVFGLWI PLVVAIYYVY IESWTLGFAI 
121:	KFLVGLVPEP PPNATDPDSI LRPFKEFLYS YIGVPKGDEP ILKPSLFAYI VFLITMFINV 
181:	SILIRGISKG IERFAKIAMP TLFILAVFLV IRVFLLETPN GTAADGLNFL WTPDFEKLKD 
241:	PGVWIAAVGQ IFFTLSLGFG AIITYASYVR KDQDIVLSGL TAATLNEKAE VILGGSISIP 
301:	AAVAFFGVAN AVAIAKAGAF NLGFITLPAI FSQTAGGTFL GFLWFFLLFF AGLTSSIAIM 
361:	QPMIAFLEDE LKLSRKHAVL WTAAIVFFSA HLVMFLNKSL DEMDFWAGTI GVVFFGLTEL 
421:	IIFFWIFGAD KAWEEINRGG IIKVPRIYYY VMRYITPAFL AVLLVVWARE YIPKIMEETH 
481:	WTVWITRFYI IGLFLFLTFL VFLAERRRNH ESA