Characterization of Ghrelin O-acyltransferase Active Site

Author

Leslie Patton, Syracuse UniversityFollow

Bound Volume Number

1

Degree Type

Honors Capstone Project

Date of Submission

Spring 5-1-2015

Capstone Advisor

Prof. James Hougland

Honors Reader

Prof. Heather Coleman

Capstone Major

Biology

Capstone College

Arts and Science

Audio/Visual Component

no

Keywords

Alzheimer’s, Parkinson’s, obesity, diabetes, ghrelin peptide, chromatography

Capstone Prize Winner

no

Won Capstone Funding

yes

Honors Categories

Sciences and Engineering

Subject Categories

Amino Acids, Peptides, and Proteins | Biochemical Phenomena, Metabolism, and Nutrition | Biochemistry | Cell Biology | Molecular Biology

Abstract

Ghrelin, first discovered in 1999, is a 28-amino acid peptide hormone involved in the regulation of appetite, insulin secretion and sensitivity, and many neurological effects such as learning, memory, and depression.^1-6 Ghrelin has been identified to have a unique posttranslational octanoylation carried out by the enzyme ghrelin O-acyltransferase (GOAT). This distinctive modification is a point of interest in studying GOAT whereby blocking the acylation of the ghrelin could potentially halt the activity of the peptide hormone and provide a means of treating obesity, diabetes, and other diseases affected by ghrelin levels. The duration of my project involved working with a 20-amino acid mimic of the ghrelin peptide with various single residue mutations in the original wild type ghrelin sequence (GSSFLSPEHQRVQQRKESKK). The 20-amino acid ghrelin mimics are fluorescently labeled with a single acrylodan compound, and the activity as well as the inhibitory effects are monitored via reverse phase high performance liquid chromatography.⁷ Further studies were done to identify the interactions of ghrelin with GOAT specifically at the N-terminal lysine-5 position of ghrelin. Defining the interactions of ghrelin with the GOAT binding site and octanoyl Co-A substrates would pave the way to design inhibitors and aid in helping diseases related to diabetes, obesity, and neurological illnesses such as Alzheimer’s and Parkinson’s.

Recommended Citation

Patton, Leslie, "Characterization of Ghrelin O-acyltransferase Active Site" (2015). Honors Capstone Projects - All. 823.
https://surface.syr.edu/honors_capstone/823

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.