Defense Date
12-10-2011
Graduation Date
2011
Availability
Immediate Access
Submission Type
dissertation
Degree Name
PhD
Department
Pharmacology-Toxicology
School
School of Pharmacy
Committee Chair
Christopher K. Surratt
Committee Member
Jeffry Madura
Committee Member
Paula A. Witt-Enderby
Committee Member
David A. Johnson
Committee Member
Wilson S. Meng
Keywords
Dopamine transporter, Molecular model, Mutagenesis, Photoaffinity labeling, Virtual screening
Abstract
The dissertation will give an introduction, background and our research progress in the areas of dopamine transporter (DAT). A 3-D DAT computer model was generated in our laboratory based on the X-ray crystal structure of the bacterial leucine transporter LeuT, a distant homolog of DAT. The ability of this LeuTAa-based 3-D DAT computer model to identify specific DAT residues involved in inhibitor recognition was assessed through site-directed mutagenesis and subsequent pharmacologic characterization in the present study. Feedback from these experiments confirmed some of the suggestion from the DAT model, which is encouraging that the comparative DAT model is valid to some extent and could be further used for ligand docking and virtual screening.
Format
Language
English
Recommended Citation
Liu, Y. (2011). Structural Determinants for Inhibitor Recognition by the Dopamine Transporter (Doctoral dissertation, Duquesne University). Retrieved from https://dsc.duq.edu/etd/829