Mechanistic aspects of sodium-binding sites in LeuT-like fold symporters
نویسندگان
چکیده
منابع مشابه
Substrate and drug binding sites in LeuT.
LeuT is a member of the neurotransmitter/sodium symporter family, which includes the neuronal transporters for serotonin, norepinephrine, and dopamine. The original crystal structure of LeuT shows a primary leucine-binding site at the center of the protein. LeuT is inhibited by different classes of antidepressants that act as potent inhibitors of the serotonin transporter. The newly determined ...
متن کاملChloride binding site of neurotransmitter sodium symporters.
Neurotransmitter:sodium symporters (NSSs) play a critical role in signaling by reuptake of neurotransmitters. Eukaryotic NSSs are chloride-dependent, whereas prokaryotic NSS homologs like LeuT are chloride-independent but contain an acidic residue (Glu290 in LeuT) at a site where eukaryotic NSSs have a serine. The LeuT-E290S mutant displays chloride-dependent activity. We show that, in LeuT-E29...
متن کاملDirect assessment of substrate binding to the Neurotransmitter:Sodium Symporter LeuT by solid state NMR
The Neurotransmitter:Sodium Symporters (NSSs) represent an important class of proteins mediating sodium-dependent uptake of neurotransmitters from the extracellular space. The substrate binding stoichiometry of the bacterial NSS protein, LeuT, and thus the principal transport mechanism, has been heavily debated. Here we used solid state NMR to specifically characterize the bound leucine ligand ...
متن کاملTo be, or not to be two sites: that is the question about LeuT substrate binding
Transport proteins of the neurotransmitter sodium symporter (NSS) family regulate the extracellular concentration of several neurotransmitters in the central nervous system. The only member of this family for which atomic-resolution structural data are available is the prokaryotic homologue LeuT. This protein has been used as a model system to study the molecular mechanism of transport of the N...
متن کاملSubstrate-dependent proton antiport in neurotransmitter:sodium symporters
Neurotransmitter-sodium symporters (NSS), targets for psychostimulants and therapeutic drugs, have a critical role in neurotransmission. Whereas eukaryotic NSS show chloride-dependent transport, bacterial NSS feature Cl(-)-independent substrate transport. Recently we showed that mutation of an acidic residue near one of the sodium ion-binding sites in LeuT of Aquifex aeolicus or Tyt1 of Fusobac...
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ژورنال
عنوان ژورنال: Biological Chemistry
سال: 2013
ISSN: 1437-4315,1431-6730
DOI: 10.1515/hsz-2012-0336