Title : Role of aromatic transmembrane residues of the organic anion transporter, rOAT3, in substrate recognition.

Pub. Date : 2002 Jul 16

PMID : 12102636






18 Functional Relationships(s)
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1 The rat organic anion transporter, rOAT3, mediates the transport of organic anions such as p-aminohippurate (PAH) and estrone sulfate as well as the basic compound, cimetidine. p-Aminohippuric Acid solute carrier family 22 member 8 Rattus norvegicus
2 The rat organic anion transporter, rOAT3, mediates the transport of organic anions such as p-aminohippurate (PAH) and estrone sulfate as well as the basic compound, cimetidine. p-Aminohippuric Acid solute carrier family 22 member 8 Rattus norvegicus
3 The rat organic anion transporter, rOAT3, mediates the transport of organic anions such as p-aminohippurate (PAH) and estrone sulfate as well as the basic compound, cimetidine. estrone sulfate solute carrier family 22 member 8 Rattus norvegicus
4 The rat organic anion transporter, rOAT3, mediates the transport of organic anions such as p-aminohippurate (PAH) and estrone sulfate as well as the basic compound, cimetidine. Cimetidine solute carrier family 22 member 8 Rattus norvegicus
5 In the present study, we examined the role of conserved transmembrane aromatic amino acid residues of rOAT3 in substrate recognition and transport. Amino Acids, Aromatic solute carrier family 22 member 8 Rattus norvegicus
6 Alanine scanning followed by amino acid replacements was used to construct mutants of rOAT3. Alanine solute carrier family 22 member 8 Rattus norvegicus
7 We observed that four mutants in transmembrane domain 7 (TMD 7), W334A, F335A, Y341A, and Y342Q, and one mutant in transmembrane domain 8 (TMD 8), F362S, exhibited a less than 2-fold enhanced uptake of PAH and cimetidine in comparison to wild-type rOAT3, which exhibited a 16-fold enhanced uptake of PAH and an 8-fold enhanced uptake of cimetidine. p-Aminohippuric Acid solute carrier family 22 member 8 Rattus norvegicus
8 We observed that four mutants in transmembrane domain 7 (TMD 7), W334A, F335A, Y341A, and Y342Q, and one mutant in transmembrane domain 8 (TMD 8), F362S, exhibited a less than 2-fold enhanced uptake of PAH and cimetidine in comparison to wild-type rOAT3, which exhibited a 16-fold enhanced uptake of PAH and an 8-fold enhanced uptake of cimetidine. Cimetidine solute carrier family 22 member 8 Rattus norvegicus
9 We observed that four mutants in transmembrane domain 7 (TMD 7), W334A, F335A, Y341A, and Y342Q, and one mutant in transmembrane domain 8 (TMD 8), F362S, exhibited a less than 2-fold enhanced uptake of PAH and cimetidine in comparison to wild-type rOAT3, which exhibited a 16-fold enhanced uptake of PAH and an 8-fold enhanced uptake of cimetidine. p-Aminohippuric Acid solute carrier family 22 member 8 Rattus norvegicus
10 We observed that four mutants in transmembrane domain 7 (TMD 7), W334A, F335A, Y341A, and Y342Q, and one mutant in transmembrane domain 8 (TMD 8), F362S, exhibited a less than 2-fold enhanced uptake of PAH and cimetidine in comparison to wild-type rOAT3, which exhibited a 16-fold enhanced uptake of PAH and an 8-fold enhanced uptake of cimetidine. Cimetidine solute carrier family 22 member 8 Rattus norvegicus
11 We observed that the residues contribute to PAH and cimetidine transport in different ways: the -OH group of Y342, the indole ring of W334, and the aromatic rings of F335, Y341, and F362 are important for PAH and cimetidine transport by rOAT3. p-Aminohippuric Acid solute carrier family 22 member 8 Rattus norvegicus
12 We observed that the residues contribute to PAH and cimetidine transport in different ways: the -OH group of Y342, the indole ring of W334, and the aromatic rings of F335, Y341, and F362 are important for PAH and cimetidine transport by rOAT3. Cimetidine solute carrier family 22 member 8 Rattus norvegicus
13 We observed that the residues contribute to PAH and cimetidine transport in different ways: the -OH group of Y342, the indole ring of W334, and the aromatic rings of F335, Y341, and F362 are important for PAH and cimetidine transport by rOAT3. indole solute carrier family 22 member 8 Rattus norvegicus
14 We observed that the residues contribute to PAH and cimetidine transport in different ways: the -OH group of Y342, the indole ring of W334, and the aromatic rings of F335, Y341, and F362 are important for PAH and cimetidine transport by rOAT3. p-Aminohippuric Acid solute carrier family 22 member 8 Rattus norvegicus
15 We observed that the residues contribute to PAH and cimetidine transport in different ways: the -OH group of Y342, the indole ring of W334, and the aromatic rings of F335, Y341, and F362 are important for PAH and cimetidine transport by rOAT3. Cimetidine solute carrier family 22 member 8 Rattus norvegicus
16 These data suggest that there is an aromatic pocket composed mainly of residues in TMD 7 in the translocation pathway of rOAT3, which is important for the transport of PAH and cimetidine. p-Aminohippuric Acid solute carrier family 22 member 8 Rattus norvegicus
17 These data suggest that there is an aromatic pocket composed mainly of residues in TMD 7 in the translocation pathway of rOAT3, which is important for the transport of PAH and cimetidine. Cimetidine solute carrier family 22 member 8 Rattus norvegicus
18 Aromatic residues in this pocket may interact directly with substrates of rOAT3 through hydrogen bonds and pi-pi interactions. Hydrogen solute carrier family 22 member 8 Rattus norvegicus