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Sulfated Glycoconjugates
Biosynthesis, Control, and Regulation
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Regulation Glycobiology What do we know?
Complex mechanism of regulation Ongoing research What do we know? Proteoglycans require O-linked glycosylation Biosynthesis occurs in ER and GA Tetrasaccharide linkage unique to proteoglycans Unique linear, unbranched Glycosaminoglycan (GAG) Sulfation and other modifications occur at the end of proteoglycan synthesis
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Proteoglygan structure
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Route of proteoglycan synthesis
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Tetrasaccharide linkgage
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UDP-GlcA Transferase I Mechanism
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Heparan Sulfate/Heparin
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Heparan Sulfate/Heparin
Know sulfation mechanism, catalyze the inversion of stereochemistry in biological molecules
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Chondroitin Sulfate/Dermatan Sulfate
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Keratan Sulfate
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Ongoing Research Still unclear: How serine is selected
What factors determine how long GAG chains polymerize Organization of the enzymes of the GA compartment and how they are regulated
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References Kusche-Gullberg, Marion. Kjellén, Lena “Sulfotransferases in glycosaminoglycan biosynthesis” Current Opinion in Structural Biology. Volume 13, Issue 5, October 2003, Prydz1, Kristian. Dalen, Knut Tomas. “Synthesis and sorting of proteoglycans” Journal of Cell Science 113, (2000) Aberts, Bruce. Johnson, Alexander. Lewis, Julian. Raff, Martin. Roberts, Keith. Walter, Peter.“Molecular Biology of The Cell” 5th edition. 2008
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