Non-lectin type Protein-carbohydrate Interactions: A Structural Perspective
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The Ohio State University / OhioLINK
2011
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=osu1306858684 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu13068586842021-08-03T06:02:58Z Non-lectin type Protein-carbohydrate Interactions: A Structural Perspective Bhatt, Veer Sandeep Biochemistry Biomedical Engineering Biophysics Protein-carbohydrate interaction protein glycosylation protein structure X-ray crystallography UDP-hexose 4-epimerase Rossmann fold Hemoglobin Lipopolysaccharide Wzy Wzz WaaL Heteropolysaccharide Oxygen affinity Protein-carbohydrate interactions are critical in a multitude of life processes such as bioenergetics, inflammation, cell-cell recognition, cell differentiation, embryonic development, signal transduction and host-pathogen interactions. However, the events leading to protein-carbohydrate recognition and the modulation of protein activity by glycosylation are poorly understood at molecular level. The primary objective in this work is to enrich our understanding of protein-carbohydrate interactions at a molecular level using three model systems. The first system is that of hemoglobin. The modulation of oxygen affinity by various interactions at the quaternary level is first presented in an investigation of the high oxygen affinity Greyhound hemoglobin. This is followed by a structural investigation of bovine hemoglobin carrying different lengths and types of oligosaccharides. These investigations indicate that glycosylation can increase the intrinsic oxygen affinity of hemoglobin by modifying its quaternary structure. The second system is that of a carbohydrate processing enzyme, a uridine 5'-diphospho N-acetylgalactosamine 4-epimerase. An elaborate investigation of structure and and activity of this enzyme reveals several novel details of substrate recognition that may have been overlooked previously. Notably, this investigation highlights the complexities of protein-carbohydrate recognition and provides evidence that carbohydrates by themselves may induce global changes in multi-domain proteins. It further indicates that non-polar interactions are also critical in mediating protein-carbohydrate interactions and should be given due consideration in applications such as carbohydrate-based drug discovery. Thirdly, a complex system comprising of a multi-protein machinery that regulates the size of a hetero-polysaccharide called O-antigen, is presented. This system is an essential part of lipopolysaccharide biosynthesis in Gram-negative bacteria. This investigation strongly suggests that a protein called Wzz serves as a trap for nascent oligosaccharide chains while interacting with another protein called Wzy that is responsible for polymerization of these nascent oligosaccharide chains to form the mature O-antigen. Protein X-ray crystallography and routine experimental methods of modern molecular biology such as gene cloning, expression, protein purification and characterization have been used as primary techniques in this work. In addition, computational analysis, especially to perform protein-ligand docking is also used to investigate the third system. 2011-07-27 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1306858684 http://rave.ohiolink.edu/etdc/view?acc_num=osu1306858684 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biochemistry Biomedical Engineering Biophysics Protein-carbohydrate interaction protein glycosylation protein structure X-ray crystallography UDP-hexose 4-epimerase Rossmann fold Hemoglobin Lipopolysaccharide Wzy Wzz WaaL Heteropolysaccharide Oxygen affinity |
| spellingShingle |
Biochemistry Biomedical Engineering Biophysics Protein-carbohydrate interaction protein glycosylation protein structure X-ray crystallography UDP-hexose 4-epimerase Rossmann fold Hemoglobin Lipopolysaccharide Wzy Wzz WaaL Heteropolysaccharide Oxygen affinity Bhatt, Veer Sandeep Non-lectin type Protein-carbohydrate Interactions: A Structural Perspective |
| author |
Bhatt, Veer Sandeep |
| author_facet |
Bhatt, Veer Sandeep |
| author_sort |
Bhatt, Veer Sandeep |
| title |
Non-lectin type Protein-carbohydrate Interactions: A Structural Perspective |
| title_short |
Non-lectin type Protein-carbohydrate Interactions: A Structural Perspective |
| title_full |
Non-lectin type Protein-carbohydrate Interactions: A Structural Perspective |
| title_fullStr |
Non-lectin type Protein-carbohydrate Interactions: A Structural Perspective |
| title_full_unstemmed |
Non-lectin type Protein-carbohydrate Interactions: A Structural Perspective |
| title_sort |
non-lectin type protein-carbohydrate interactions: a structural perspective |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2011 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1306858684 |
| work_keys_str_mv |
AT bhattveersandeep nonlectintypeproteincarbohydrateinteractionsastructuralperspective |
| _version_ |
1719430025576448000 |