An Investigation Into a Microbial β-Glucuronidase

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Author(s)
Primary Supervisor
Itzstein, Mark von
Other Supervisors
Beacham, Ifor
Year published
2015
Metadata
Show full item recordAbstract
Glycosaminoglycans (GAGs) are the most prevalent hetero-polysaccharides in the body. They are usually attached to a protein core, forming proteoglycans (PGs). PGs play crucial roles in a wide range of biological processes including cell growth, migration and differentiation. Heparan sulfate proteoglycans (HSPGs) are found in the basement membrane and the extracellular matrix (ECM), which surrounds cells and is formed by a network of fibrous proteins, glycoproteins and proteoglycans. In mammalian cells heparan sulfate (HS) is cleaved by a single β-glucuronidase: heparanase. Cleavage of HS-chains changes the integrity ...
View more >Glycosaminoglycans (GAGs) are the most prevalent hetero-polysaccharides in the body. They are usually attached to a protein core, forming proteoglycans (PGs). PGs play crucial roles in a wide range of biological processes including cell growth, migration and differentiation. Heparan sulfate proteoglycans (HSPGs) are found in the basement membrane and the extracellular matrix (ECM), which surrounds cells and is formed by a network of fibrous proteins, glycoproteins and proteoglycans. In mammalian cells heparan sulfate (HS) is cleaved by a single β-glucuronidase: heparanase. Cleavage of HS-chains changes the integrity of the ECM and releases a variety of bioactive molecules such as growth factors, cytokines and enzymes. Heparanase is implicated in cancer and inflammation and inhibition of heparanase has been shown to reduce tumour metastasis and angiogenesis. Heparanase is therefore regarded as a promising target for anti-cancer and anti-inflammatory drug design. As the three dimensional structure of human heparanase is still not available, the progress in specific inhibitor development has been impeded.
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View more >Glycosaminoglycans (GAGs) are the most prevalent hetero-polysaccharides in the body. They are usually attached to a protein core, forming proteoglycans (PGs). PGs play crucial roles in a wide range of biological processes including cell growth, migration and differentiation. Heparan sulfate proteoglycans (HSPGs) are found in the basement membrane and the extracellular matrix (ECM), which surrounds cells and is formed by a network of fibrous proteins, glycoproteins and proteoglycans. In mammalian cells heparan sulfate (HS) is cleaved by a single β-glucuronidase: heparanase. Cleavage of HS-chains changes the integrity of the ECM and releases a variety of bioactive molecules such as growth factors, cytokines and enzymes. Heparanase is implicated in cancer and inflammation and inhibition of heparanase has been shown to reduce tumour metastasis and angiogenesis. Heparanase is therefore regarded as a promising target for anti-cancer and anti-inflammatory drug design. As the three dimensional structure of human heparanase is still not available, the progress in specific inhibitor development has been impeded.
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Thesis Type
Thesis (PhD Doctorate)
Degree Program
Doctor of Philosophy (PhD)
School
Institute for Glycomics
Copyright Statement
The author owns the copyright in this thesis, unless stated otherwise.
Item Access Status
Public
Subject
Glycosaminoglycans (GAGs)
Hetero-polysaccharides
Proteoglycans (PGs)
Heparan sulfate proteoglycans (HSPGs)
Extracellular matrix (ECM)
Microbial β-Glucuronidase
Heparanase
Anti-cancer drugs