Problem 1: Sugars and glycoproteins (30 points) a) For each disaccharide shown below, label the anomeric...

  

 

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Problem 1: Sugars and glycoproteins (30 points) a) For each disaccharide shown below, label the anomeric carbons, and state whether it is a reducing sugar. Briefly justify your answer. (5 pts) OH OH HO- OH HO Lactose OH OH OH OH CHOH OH OH CHOH OH Sucrose HO CHOH b) Consider a molecule of amylopectin that contains 1000 glucose monomers and branches regularly after every 25 glucose residues. How many reducing ends will this amylopectin have? Explain your reasoning. (5 pts) c) of the following three subsequences, indicate which you would expect to undergo: N- glycosylation, O-glycosylation, neither of the above. Briefly (max 1 sentence per subsequence) why you assigned each subsequence to its likely glycosylation type. (6 pts) GGSSLETSTADQYSGG GGPNLGAELPQQIG Subseq. A Subseq. B Subseq. C d) Draw a structure of threonine that has been post-translationally O-glycosylated by N- Acetyl--D-galactosamine. Mark the glycosidic bond. (5 pts) GGNFSGGNVSAFGNVTAIG e) Many O-glycosylated proteins (e.g. mucins) are modified by sulfated sugars. What effect might frequent modification with sulfated sugars have on the structure of a glycoprotein? (3 pts) Problem 2: Polysaccharide in a structural study (15 pts) Heparin is widely used as a medication to treat heart attacks and unstable angina. It stimulates activity of antithrombin, that inactivates several enzymes of the coagulation system. Also, its negatively-charged feature enables researchers to purify some DNA-binding proteins (since these proteins usually harbor a large patch of positively charged surface). A report in PNAS has solved the structure of the antithrombin-factor IXa binding a pentasaccharide. a) Import the complex structure (PDB code:3KCG) into PyMOL. Show the pentasaccharide structure with "sticks". Color oxygen atoms that form glycosidic bonds in magenta. Present the resulting structure. (5 pts) b) Mark all carbohydrate residues that are in a "chair" conformation. (2 pt) c) Pentasaccharide used in this study is structurally similar to heparin. What is the most striking difference between the two? Why do you think researchers might have decided to use this pentasaccharide instead of heparin? (3 pts) Problem 1: Sugars and glycoproteins (30 points) a) For each disaccharide shown below, label the anomeric carbons, and state whether it is a reducing sugar. Briefly justify your answer. (5 pts) OH OH HO- OH HO Lactose OH OH OH OH CHOH OH OH CHOH OH Sucrose HO CHOH b) Consider a molecule of amylopectin that contains 1000 glucose monomers and branches regularly after every 25 glucose residues. How many reducing ends will this amylopectin have? Explain your reasoning. (5 pts) c) of the following three subsequences, indicate which you would expect to undergo: N- glycosylation, O-glycosylation, neither of the above. Briefly (max 1 sentence per subsequence) why you assigned each subsequence to its likely glycosylation type. (6 pts) GGSSLETSTADQYSGG GGPNLGAELPQQIG Subseq. A Subseq. B Subseq. C d) Draw a structure of threonine that has been post-translationally O-glycosylated by N- Acetyl--D-galactosamine. Mark the glycosidic bond. (5 pts) GGNFSGGNVSAFGNVTAIG e) Many O-glycosylated proteins (e.g. mucins) are modified by sulfated sugars. What effect might frequent modification with sulfated sugars have on the structure of a glycoprotein? (3 pts) Problem 2: Polysaccharide in a structural study (15 pts) Heparin is widely used as a medication to treat heart attacks and unstable angina. It stimulates activity of antithrombin, that inactivates several enzymes of the coagulation system. Also, its negatively-charged feature enables researchers to purify some DNA-binding proteins (since these proteins usually harbor a large patch of positively charged surface). A report in PNAS has solved the structure of the antithrombin-factor IXa binding a pentasaccharide. a) Import the complex structure (PDB code:3KCG) into PyMOL. Show the pentasaccharide structure with "sticks". Color oxygen atoms that form glycosidic bonds in magenta. Present the resulting structure. (5 pts) b) Mark all carbohydrate residues that are in a "chair" conformation. (2 pt) c) Pentasaccharide used in this study is structurally similar to heparin. What is the most striking difference between the two? Why do you think researchers might have decided to use this pentasaccharide instead of heparin? (3 pts)