Importance of Valine at Position 152 for the Substrate Transport and 2β-Carbomethoxy-3β-(4-fluorophenyl)tropane Binding of Dopamine Transporter

摘要: Human and bovine dopamine transporters (DAT) demonstrate discrete functional differences in (DA), 1-methyl-4-phenylpyridium (MPP+) transport, cocaine analog binding. In a previous study, the analyses on chimeras of human DAT have revealed that region from residues 133 through 186 (encompassing third transmembrane domain) is responsible for substrate transport The present study has been carried out to determine specific amino acid(s) conferring functions by interchanging acid corresponding between DAT. As described previously, DA, MPP+ 2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) binding almost disappeared chimera hb3 which was substituted into Replacement isoleucine, residue 152 (bovine sequence), with valine, at identical position, remarkably restored CFT 76% 98% values. Similarly, substitution isoleucine valine position reduced 57% 97%. Among other acids tested hb3, only alanine resulted small but significant increases ranging 16 34%. Thus, plays crucial role molecular mechanisms underlying interactions MPP+,