Ch Pi Interactions Play A Central Role In Protein Recognition Of Carbohydrates
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Ch Pi Interactions Play A Central Role In Protein Recognition Of Carbohydrates
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Author : Roger Christopher Diehl
language : en
Publisher:
Release Date : 2021
Ch Pi Interactions Play A Central Role In Protein Recognition Of Carbohydrates written by Roger Christopher Diehl and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with categories.
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.
Protein Carbohydrate And Protein Protein Interactions
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Author : Alain Teboho Laederach
language : en
Publisher:
Release Date : 2003
Protein Carbohydrate And Protein Protein Interactions written by Alain Teboho Laederach and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2003 with categories.
Any molecular recognition event results in a change in the free energy of the system. The extent of this change is related to the association constant, such that the more negative the free energy change is, the tighter the interaction between receptor and ligand. Protein-carbohydrate interactions play a critical role in signal transduction, innate immunity, and metabolism. Modeling these interactions is somewhat complicated by the inherent flexibility of carbohydrates as well as their relatively large number of functional groups. An empirical scoring function for docking carbohydrates to proteins, specifically tailored to predict both the correct binding orientation and free energy of binding of the carbohydrate-ligand/protein-receptor complex, will be presented. This new scoring function can predict free energies of binding to within 1.1 kcal/mol residual standard error, a definite improvement over existing scoring functions that result in standard errors well over 2 kcal/mol. Application of automated docking methodology to determine carbohydrate recognition specificity of the C-type lectin, human surfactant protein D, will also be presented. In the second part of the thesis, the role of [pi]-stacking interactions (e.g. between Tyr side chains) in stabilizing protein folds will be discussed. A 17-residue peptide derived from the naturally occurring anti-microbial peptide tachyplesin I was investigated using NMR spectroscopy. NOE cross-peaks were observed, confirming the existence of this interaction in solution. In the final part of the thesis, a quantitative NMR investigation into the self-association behavior of the regulatory domains of several Tec family member kinases will be presented. Of particular interest, self-association within Bruton's tyrosine kinase (Btk) regulatory domains occurs through the formation of an asymmetric homodimer. Together this work demonstrates the importance of rigorous biophysical characterization of biomolecular recognition events and the interdependence of computational modeling and experimentation.
Characterisation And Engineering Of Protein Carbohydrate Interactions
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Author : Michael Lienemann
language : en
Publisher:
Release Date : 2010
Characterisation And Engineering Of Protein Carbohydrate Interactions written by Michael Lienemann and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with Carbohydrates categories.
Protein-carbohydrate interactions play a crucial role in many biological processes such as cell-cell recognition and receptor-ligand interactions and catalysis. This thesis explores the possibilities of engineering the protein-carbohydrate interactions between carbohydrate-binding proteins and their ligands. Protein-carbohydrate interactions were characterised using different techniques, such as atomic force microscopy (AFM) and surface plasmon resonance (SPR). Two different chitinoligosaccharide-binding proteins were used in the presented experiments, i.e. the plant lectin wheat germ agglutinin (WGA) and a neolectin created by inactivation of the fungal chitin-degrading enzyme Chit42. The structures of WGA and Chit42, which were available as X-ray diffraction data and a homology model, respectively, revealed differences between their binding site architectures. The interaction of monomeric and polymeric N-acetyl-D-glucosamine (GlcNAc) with WGA, that normally binds chitinoligosaccharides on cell surfaces, was investigated with nanomechanical force measurements using AFM. These measurements aimed at determining the effect of ligand length and binding site clustering (multivalent binding) on binding strength between the protein and the carbohydrate ligand. Here, the GlcNAc ligand was presented at the surface of a planar self-assembled monolayer (SAM) of neoglycoconjugates and in a polymeric form as chitin beads. In adsorption measurements using the quartz crystal microbalance (QCM) it was shown that alkanethiols adsorb rapidly to a gold surface, covering it completely within a few minutes as an SAM. In AFM force measurements, GlcNAc-specific binding events were detected with a WGA-modified probe on a GlcNAcneoglycoconjugate SAM at bond rupture forces of 47 ± 15 pN. When this experiment was repeated on a polymeric substrate, manyfold higher forces were detected. This indicated a high increase of affinity with additional binding subsites which were able to interact with the chitinous ligand. SPR measurements confirmed that WGA has higher affinity towards the immobilized GlcNAcneoglycoconjugate SAM than towards the soluble free monosaccharide providing evidence of a significant affinity increase as a result of binding site cooperativity. Furthermore, two different SAM formats have been tested for their suitability for studying protein-carbohydrate interactions. Here, non-specific adhesion was identified as a critical factor that was mainly related to the hydrophobic parts of the neoglycoconjugates and could be attenuated by the introduction of a tetraethylene glycol spacer into the neoglycoconjugate. The binding measurements on neoglycoconjugate SAMs demonstrated that this type of carbohydrate presentation is a useful reference for interactions on naturally occurring two-dimensional glycan arrays and demonstrated that the minimization of non-specific adhesion of proteins is often required in order to obtain meaningful binding data. In addition to WGA-carbohydrate interactions this thesis also deals with the carbohydrate binding cleft of the glycoside hydrolase Trichoderma harzianum chitinase Chit42, which in the wild-type form, solubilises polymeric crystalline chitin (composed of [beta]-4 linked GlcNAc units). Nine different catalytically inactive Chit42 variants were created, carrying amino acid alterations along the binding site cleft (at sugar-binding subsites -4 to +2). These Chit42 variants were characterised with regard to their affinity towards chitinous and non-chitinous oligosaccharides by SPR. As a result, hydrogen bonding between subsites -2/-3 and particularly stacking interactions by tryptophanes at subsites -3 and +2 were seen to be very important for the carbohydrate binding. The exchange of the corresponding amino acids did not cause a change of binding specificity, although the selective binding of GlcN[beta]-4(GlcNAc)4 could be improved by providing a counter charge through an amino acid substitution at subsite -3, replacing threonine with aspartic acid. In addition the introduction of glutamine and particularly an asparagine residue at this position appeared to broaden the substrate preference towards Gal[beta]-4(GlcNAc)4, and the site was thereby implicated as a binding groove hot spot for creating binding proteins, or hydrolytic enzymes with novel substrate specificity towards e.g. structurally related and medically significant oligosaccharides. Analysis of the Chit42 variants with modified active sites showed how the binding selectivity and affinity of neolectins can be engineered and may thereby function as a model for further neolectins and glycoside hydrolases with new ligand and substrate specificities, respectively.
Glycoscience
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Author : Bertram O. Fraser-Reid
language : en
Publisher: Springer Science & Business Media
Release Date : 2008-04-14
Glycoscience written by Bertram O. Fraser-Reid and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-04-14 with Science categories.
As a reflection of the quantum leap that has been made in the study of glycostructures, the first edition of this book has been completely revised and updated. The editors give up-to-date information on glycostructures, their chemistry and chemical biology in the form of a completely comprehensive survey. Glycostructures play highly diverse and crucial roles in a myriad of organisms and important systems in biology, physiology, medicine, bioengineering and technology. Only in recent years have the tools been developed to partly understand the highly complex functions and the chemistry behind them. While many facts remain undiscovered, this MRW has been contributed to by a large number of the world’s leading researchers in the field.
Carbohydrate Recognition
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Author : Binghe Wang
language : en
Publisher: John Wiley & Sons
Release Date : 2011-09-09
Carbohydrate Recognition written by Binghe Wang and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-09-09 with Medical categories.
This book contains contributions from interdisciplinary scientists to collectively address the issue of targeting carbohydrate recognition for the development of novel therapeutic and diagnostic agents. The book covers (1) biological problems involving carbohydrate recognition, (2) structural factors mediating carbohydrate recognition, (3) design and synthesis of lectin mimics that recognize carbohydrate ligands with high specificity and affinity, and (4) modulation of biological and pathological processes through carbohydrate recognition.
The Fragment Molecular Orbital Method
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Author : Dmitri Fedorov
language : en
Publisher: CRC Press
Release Date : 2009-05-14
The Fragment Molecular Orbital Method written by Dmitri Fedorov and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-05-14 with Science categories.
Answering the need to facilitate quantum-chemical calculations of systems with thousands of atoms, Kazuo Kitaura and his coworkers developed the Fragment Molecular Orbital (FMO) method in 1999. Today, the FMO method can be applied to the study of whole proteins and protein-ligand interactions, and is extremely effective in calculating the propertie
Carbohydrate Chemistry
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Author : Amelia Pilar Rauter
language : en
Publisher: Royal Society of Chemistry
Release Date : 2015-12-02
Carbohydrate Chemistry written by Amelia Pilar Rauter and has been published by Royal Society of Chemistry this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-12-02 with Science categories.
With the increase in volume, velocity and variety of information, researchers can find it difficult to keep up to date with the literature in the field. As the synthesis of novel carbohydrates and carbohydrate mimetics continues to be a major challenge for organic chemists, not least because of the increasingly interdisciplinary nature of carbohydrate science, Carbohydrate Chemistry Volume 41 will prove invaluable. Covering both chemical and biological science, this series collates modern carbohydrate research from theory to application and will be of great benefit to any researcher who wishes to learn about the latest developments in the carbohydrate field.
Carbohydrate Chemistry Chemical And Biological Approaches Volume 44
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Author : Amelia Pilar Rauter
language : en
Publisher: Royal Society of Chemistry
Release Date : 2020-10-06
Carbohydrate Chemistry Chemical And Biological Approaches Volume 44 written by Amelia Pilar Rauter and has been published by Royal Society of Chemistry this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-10-06 with Science categories.
Carbohydrate Chemistry is an invaluable volume demonstrating the interdisciplinary nature of modern carbohydrate research and containing analysed, evaluated and distilled information on the latest research in the area.
Transforming Glycoscience
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Author : National Research Council
language : en
Publisher: National Academies Press
Release Date : 2012-10-23
Transforming Glycoscience written by National Research Council and has been published by National Academies Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-10-23 with Science categories.
A new focus on glycoscience, a field that explores the structures and functions of sugars, promises great advances in areas as diverse as medicine, energy generation, and materials science, this report finds. Glycans-also known as carbohydrates, saccharides, or simply as sugars-play central roles in many biological processes and have properties useful in an array of applications. However, glycans have received little attention from the research community due to a lack of tools to probe their often complex structures and properties. Transforming Glycoscience: A Roadmap for the Future presents a roadmap for transforming glycoscience from a field dominated by specialists to a widely studied and integrated discipline, which could lead to a more complete understanding of glycans and help solve key challenges in diverse fields.
Computational Tools For Chemical Biology
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Author : Sonsoles Martín-Santamaría
language : en
Publisher: Royal Society of Chemistry
Release Date : 2017-11-01
Computational Tools For Chemical Biology written by Sonsoles Martín-Santamaría and has been published by Royal Society of Chemistry this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-11-01 with Science categories.
This book offers a fresh perspective on how computational tools can aid the chemical biology research community and drive new research.