Organic anion transporters (OATs, SLC21) are important in the excretion of endogenous and exogenous compounds in the kidney. The @entity35 @entity24072 , @entity15823 , mediates the transport of organic anions such as @entity10945 ( @entity2556 ) and @entity19517 as well as the basic compound, @entity4444 . In the present study, we examined the role of conserved transmembrane aromatic @entity535 residues of @entity15823 in substrate recognition and transport. @entity493 scanning followed by @entity535 replacements was used to construct mutants of @entity15823 . The uptake of model compounds was studied in @entity1238 oocytes expressing the mutant transporters. We observed that four mutants in transmembrane domain 7 ( @entity9321 7), W334A, @entity53453 , @entity68985 , and @entity68986 , and one mutant in transmembrane domain 8 ( @entity9321 8), @entity68987 , exhibited a less than 2-fold enhanced uptake of @entity2556 and @entity4444 in comparison to wild-type @entity15823 , which exhibited a 16-fold enhanced uptake of @entity2556 and an 8-fold enhanced uptake of @entity4444 . @entity19517 uptake in oocytes expressing any one of these five mutants remained at least 8-fold enhanced. The data suggest that the five residues, W334, F335, Y341, Y342, and F362, contribute differently to the transport of the small hydrophilic organic substrates @entity2556 and @entity4444 in comparison to the large hydrophobic organic substrate @entity19517 . The effects of side chains of these five residues on transporter functions were also evaluated by constructing conservative mutations. We observed that the residues contribute to @entity2556 and @entity4444 transport in different ways: the - @entity2145 group of Y342, the @entity104 ring of W334, and the aromatic rings of F335, Y341, and F362 are important for @entity2556 and @entity4444 transport by @entity15823 . These data suggest that there is an aromatic pocket composed mainly of residues in @entity9321 7 in the translocation pathway of @entity15823 , which is important for the transport of @entity2556 and @entity4444 . Aromatic residues in this pocket may interact directly with substrates of @entity15823 through @entity3884 bonds and pi-pi interactions.

Role of aromatic transmembrane residues of the @entity24072 , XXXX , in substrate recognition.

@entity4444 :: ('MESH:D002927', 'Chemical') :: ['cimetidine'] @entity53453 :: ('p|SUB|F|335|A', 'ProteinMutation') :: ['F335A'] @entity24072 :: ('140668(Tax:10116)', 'Gene') :: ['organic anion transporter'] @entity9321 :: ('MESH:D049310', 'Disease') :: ['TMD'] @entity19517 :: ('MESH:C017296', 'Chemical') :: ['estrone sulfate', 'Estrone sulfate'] @entity1238 :: ('8355', 'Species') :: ['Xenopus laevis'] @entity68985 :: ('p|SUB|Y|341|A', 'ProteinMutation') :: ['Y341A'] @entity10945 :: ('MESH:D010130', 'Chemical') :: ['p-aminohippurate'] @entity535 :: ('CHEBI:33704', 'Chemical') :: ['amino acid'] @entity3884 :: ('MESH:D006859', 'Chemical') :: ['hydrogen'] @entity2556 :: ('CHEBI:33848', 'Chemical') :: ['PAH'] @entity15823 :: ('83500(Tax:10116)', 'Gene') :: ['rOAT3'] @entity68986 :: ('p|SUB|Y|342|Q', 'ProteinMutation') :: ['Y342Q'] @entity68987 :: ('p|SUB|F|362|S', 'ProteinMutation') :: ['F362S'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity493 :: ('CHEBI:16449', 'Chemical') :: ['Alanine'] @entity2145 :: ('MESH:C031356', 'Chemical') :: ['OH'] @entity104 :: ('MESH:C030374', 'Chemical') :: ['indole']
@entity15823 :: (83500(Tax:10116),Gene) :: ['rOAT3']
