lecture 31 - glycan binding proteins - GAG proteins

Question 1

what do glycan bidning proteins bind?

Answer 1

glycans (polysaccarides, carbohydrates)

Question 2

what are the two groups of glycan bidning proteins?

what does this group exclude?

Answer 2

• lectins and glycosaminoglycan binding (GAG) proteins

- excludes glycan specific antibodies

Question 3

describe GAG proteins

Answer 3

• linear polysaccarides made of disaccaride building blocks
• disaccaride = [amino sugar (glucosamine with N-acylat’n, N-sulfain or N-acetyl galactosamine)] + [uronic acid (glucouronic or iduronic acid) or galactose]
• usually long polysaccaride chains (n=40-50+)

Question 4

explain proteoglycans

Answer 4

• there are several GAG proteins found on a protein core

- protein core + GAGs = proteoglycan

Question 5

are GAGs anionic? why or why not? are there exceptions to this rule?

Answer 5

• highly anionic
• bc have carboxylate grps and many are highly sulfated on the O- or N-
• hyaluronic acid (no sulfate grps)

Question 6

GAG binding proteins (BPs) are classified into subgroups based on what? provide an e.g.

Answer 6

• the type of GAG they recognize

- e.g. heparin sulfate BPs, keratin sulfate BPs, etc.

Question 7

are most GAG BPs evolutionarily related? why or why not?

Answer 7

• no

- do not have common folds

Question 8

what is found at the binding site of GAG proteins?

Answer 8

• clusters of basic, positively charged amino acids

- usually lys/arg

Question 9

what do GAG binding proteins bind specifically?

Answer 9

• bind a specific arrangement of carboxylic acid and sulfate groups on the GAG chain
• typically internal on an extended GAG chain (not ends)
• these regions can recur in the chain

Question 10

describe the binding of GAG BPs

Answer 10

binding tends to be monovalent (one carbon to one protein) with high affinity

Question 11

antithrombin has what type of activity? for what?

Answer 11

• protease inhibiting activity

- for thrombin or factor Xa

Question 12

explain the use of heparin in medicine

Answer 12

used frequently in medicine as an anticoagulant

Question 13

antithrombin can inhibit what?

Answer 13

heparin or heparin sulfates

Question 14

explain what happens to the reactive center loop when antithrombin interacts with heparin/heparin sulfates

Answer 14

the interaction makes this reactive site more flexible, allowing antithrombin to be activated, and conduct its protease activity

Question 15

explain the relationship between the D helix and A helix of antithrombin

Answer 15

• the D helix has many positive residues on one face of the helix that are also in close proximity to the args in the A helix
• this allows the protein to interact with negatively charged heparins/heparin sulfates

Question 16

what is the minimum requirement for antithrombin activation towards thrombin?

Answer 16

• minimum of 18 monosacharide residues

- proper arrangment of carboxylic acid/sulfate groups

Question 17

what is the minimum requirement for antithrombin activation towards FXa?

Answer 17

• pentasaccaride binding is sufficient for activity

- proper arrangement of carboxylic acid/sulfate grps