CH-[pi] Interactions Play a Central Role in Protein Recognition of Carbohydrates PDF Download

Author: Roger Christopher Diehl
Publisher:
ISBN:
Category :
Languages : en
Pages : 102

Get Book

Book Description
Carbohydrate-protein interactions play a central role in biology, but knowledge of the forces underlying them is limited. Carbohydrates are generally hydrophilic and therefore present unique challenges in their recognition. One underappreciated force involved in carbohydrate-protein interactions is the CH-[pi] interaction, an attractive interaction between the aliphatic protons of a carbohydrate and the [pi] system of an aromatic ring. In this thesis, I examine the fundamental nature, strength, and biological significance of this interaction, largely in the context of a family of carbohydrate-binding proteins known as galectins. In Chapter 1, I review previous knowledge of the forces underlying carbohydrate-binding proteins and the forces they utilize to bind their ligands. In particular, I focus on CH-[pi] interactions and galectins. In Chapter 2, I examine the forces that contribute to CH-[pi] interactions in the context of carbohydrates and aromatic compounds in aqueous solution. I find the CH-[pi] interaction to be electronic in nature, and demonstrate its selectivity between different carbohydrates. In Chapter 3, I determine the contribution of the CH-[pi] interaction to the ligand binding of galectin-3, a human carbohydrate-binding protein of medical significance. The data demonstrate that the CH-[pi] interaction accounts for a majority of the binding energy. In Chapter 4, I explore the biological implications of the CH-[pi] interaction in galectin-3. I demonstrate that the CH-[pi] interaction is critical for the biological activities of galectin-3. In Chapter 5, I propose several directions future researchers could take to extend this work. For three of four directions, I present the progress I have made during my studies. The work contained within this thesis demonstrates that CH-[pi] interactions play a central role in protein-carbohydrate interactions at both a molecular level and a biological level. Understanding the CH-[pi] interaction is key to explaining and predicting the activity of carbohydrate-binding proteins.