The functional domains of dopamine transporter for cocaine analog, CFT binding.
- Author:
Sang Hun LEE
1
;
Mi Yoon CHANG
;
Dae Joon JEON
;
Dong Yul OH
;
Hyeon SON
;
Chang Ho LEE
;
Young Seek LEE
;
Yong Sung LEE
Author Information
1. Department of Biochemistry, College of Medicine, Hanyang University, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- MeSH:
Animal;
Cattle;
Chimeric Proteins/genetics/metabolism;
Cocaine/*analogs & derivatives/*metabolism;
Human;
Membrane Transport Proteins/*genetics/*metabolism;
Protein Binding;
Protein Structure, Tertiary
- From:Experimental & Molecular Medicine
2002;34(1):90-94
- CountryRepublic of Korea
- Language:English
-
Abstract:
Cocaine analogue, CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane) binding to dopamine transporter (DAT) in different species is quite heterogeneous. CFT is scarcely detected in bovine DAT whereas it is conspicuous in humans. To examine the structural basis for this functional discrepancy, we analyzed transporter chimeras of these two DATs. The CFT binding activities are avid in all of the chimeric DATs of which both of the 3rd and the 6-8th transmembrane domain (TM) are composed of human DAT sequences. On the contrary, CFT binding activities were scarcely detected if either or both of two regions are replaced with bovine sequences. These findings indicate that the CFT binding absolutely requires human DAT sequences, at least, in the regions encompassing the 3rd and 6-8th transmembrane domain (TM), and that these regions might contribute to form the 3-dimensional pocket for CFT binding.
