Date of Award

2013

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

Advisor(s)

Coleman, Heather

Keywords

hGOAT, Ghrelin

Subject Categories

Chemistry

Abstract

Ghrelin is a peptide hormone involved in appetite stimulation, regulation of insulin signaling, and other physiological processes. Ghrelin requires acylation of the hydroxyl group of a specific serine residue with an octanoyl group to bind its receptor and activate signaling. This modification is catalyzed by ghrelin O-acyltransferase (GOAT). Ghrelin is the only known substrate of GOAT, making GOAT inhibition a promising avenue for treatment of obesity and type II diabetes. Understanding the interactions between ghrelin and GOAT responsible for binding and catalysis will aid in developing specific GOAT inhibitors. To identify the nature and location of the ghrelin binding site and active site within human GOAT (hGOAT), we have generated a series of hGOAT mutants. The ghrelin acylation activity of these mutants will be tested to ascertain which regions of hGOAT are essential for function. To develop a profile of the binding site for the acyl-coenzyme A cosubstrate of hGOAT, acyl CoA donors with varying acyl lengths were tested for ghrelin acylation activity with hGOAT. Identifying the hGOAT active site and substrate binding site will aid in hGOAT characterization and provide information for development of hGOAT inhibitors.

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Open Access

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