Mechanism and Putative Structure of B0-like Neutral Amino Acid Transporters
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The Na+-dependent transport of neutral amino acids in epithelial cells and neurons is mediated by B0-type neutral amino acid transporters. Two B0-type amino acid transporters have been identified in the neurotransmitter transporter family SLC6, namely B0AT1 (SLC6A19) and B0AT2 (SLC6A15). In contrast to other members of this family, B0-like transporters are chloride-independent. B0AT1 and B0AT2 preferentially bind the substrate prior to the Na+-ion. The Na+-concentration affects the K m of the substrate and vice versa. A kinetic scheme is proposed that is consistent with the experimental data. An overlapping binding site of substrate and cosubstrate has been demonstrated in the bacterial orthologue LeuT Aa from Aquifex aeolicus, which elegantly explains the mutual effect of substrate and cosubstrate on each other’s K m -value. LeuT Aa is sequence-related to transporters of the SLC6 family, allowing homology modeling of B0-like transporters along its structure.
KeywordsHartnup disorder Neurotransmitter transporter Structure modeling SLC6A19 SLC6A15
Work in the laboratory of the authors is supported by grants from the Australian Research Council (ARC) and the National Health and Medical Research Council (NHMRC).
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