Mechanism and putative structure of B(0)-like neutral amino acid transporters.
The Na(+)-dependent transport of neutral amino acids in epithelial cells and neurons is mediated by B(0)-type neutral amino acid transporters. Two B(0)-type amino acid transporters have been identified in the neurotransmitter transporter family SLC6, namely B(0)AT1 (SLC6A19) and B(0)AT2 (SLC6A15). In contrast to other members of this family, B(0)-like transporters are chloride-independent. B(0)AT1 and B(0)AT2 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 B(0)-like transporters along its structure.
O'Mara
M
M
Department of Biological Sciences, University of Calgary, 2500 University Dr. NW, Calgary, Alberta, Canada, T2N 1N4.
Oakley
A
A
Bröer
S
S
D000595:Amino Acid Sequence; D026921:Amino Acid Transport Systems, Neutral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D026921:Amino Acid Transport Systems, Neutral; D001426:Bacterial Proteins; D011994:Recombinant Proteins