Protein-Carbohydrate Interactions

Abstract

All rights reserved INFORMATION TO ALL USERSThe quality of this reproduction is d e p e n d e n t upon the quality of the copy subm itted.In the unlikely e v e n t that the a u thor did not send a c o m p le te m anuscript and there are missing pages, these will be noted. Also, if m aterial had to be rem oved, a n o te will ind ica te the deletion. uestProQuest 10171019Published by ProQuest LLO (2017). C opyright of the Dissertation is held by the Author. In submitting this thesis to the University of St. Andrews I understand that I am giving permission for it to be made available for use in accordance with the regulations of the University Library for the time being in force, subject to any copyright vested in the work not being affected thereby. I also understand that the title and abstract will be published, and that a copy of the work may be made and supplied to any bona fide library or research worker. 15Acknowledgements.Firstly, thanks go to my supervisor Jim Naismith for his constant enthusiasm and encouragement over the past three years, and for helping me to achieve my goals. Thanks also go to Steve Homans, JTrevor Rutherford, Charlie Weller and Tony Chiovotti for useful discussions. A special thanks goes to everyone in the Naismith group, especiallyStephen for making the lab a good place to work.Thanks are not enough for my parents, they are truly amazing.Finally, a special thanks goes to Alex, who achieved the impossible and made the sun shine every day in St. Andrews. 16Chapter 1Protein -Carbohydrate Interactions. 17 SummaryCarbohydrates are ubiquitous in biological systems. A sophisticated array of these molecules are found on cell surfaces and they are recognised with varying degrees of specificities by carbohydrate binding proteins such as lectins, anti-carbohydrate antibodies, bacterial periplasmic binding proteins and some enzymes. The interactions between proteins and carbohydrates are attractive therapeutic targets. However, the ubiquity of carbohydrates presents a huge challenge for rational design of therapeutics.The physical basis of protein -carbohydrate interactions is still too poorly understood to permit such design. Improving our understanding needs an atomic level understanding of the recognition of a carbohydrate by a protein. In recent years. X-ray crystallography together with isothermal titration microcalorimetry has begun to provide a powerful insight into the molecular processes governing protein -carbohydrate interactions. This chapter will summarise the current information available from X-ray structures and thermodynamics studies, identifying common features of protein -carbohydrate interactions.Concanavalin A from the Jack bean {Canavalia enisform is\ is the most well studied lectin. It was the first of the lectins to have its three dimensional structure solved by Xray crystallography, the first to have a carbohydrate bound structure solved and the first lectin to be solved to atomic resolution. The thermodynamics of its binding to both natural and modified carbohydrates ...