Theses and Dissertations

Date of Award

12-2015

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Dr. Evangelia Kotsikorou

Second Advisor

Dr. Frank Dean

Third Advisor

Dr. James Bullard

Abstract

GPR119 receptor’s biological role in regulating glucose homeostasis has been studied extensively. Results in the scientific literature indicate that, when activated, GPR119 releases insulin in a glucose dependent manner. Currently the 3D structure of GPR119 has not been resolved.

The goal of this research is to use a combination of homology modeling and ligand docking studies to predict the binding mode of GPR119 ligands. Amino acids implicated to have direct interactions with docked ligands will further be assessed experimentally for their roll in binding and activation of GPR119. Our results indicate that residues W2656.48 and R813.28 are likely to be directly involved in ligand binding and activation of the GPR119 receptor. In addition, the R2627.36 mutant did not show any involvement in receptor binding or activation. Understanding how GPR119 interacts with its ligands can lead to the development of more effective and selective drugs that are used to treat T2D.

Comments

Copyright 2015 Shane M. Askar. All Rights Reserved.

https://www.proquest.com/dissertations-theses/molecular-modeling-mutational-mapping-gpr119/docview/1771508820/se-2?accountid=7119

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