12 - Post-Translational Modification

Question 1

post-translational modificaton

Answer 1

catalyzed by enzymes that serve as binding sites

Question 2

protein degradation

Answer 2

degradation of intracellular proteins of eukaryotes with UPS

Question 3

ubiquitin-protesome system (UPS) mechanism

Answer 3

1. target protein is monoubiquinated as the C-terminus of the ubiquitin attacks the N-terminus at target protein
2. polyubiquination occurs as the C-terminus of a new ubiquitin attacks the N-terminus of the lysine on the previous ubiquiton
3. polyubiquinated target protein is now marked for destruction

Question 4

ubiquitin

Answer 4

small protein found in all eukaryotes that can be linked to a target protein to tag it for destruction

Question 5

E1 and E2

Answer 5

activates free ubiquitin with high thioester bond

Question 6

E3

Answer 6

recognizes the target protein, coordinating it with E2 to be ubiquinated

Question 7

PROteolysis TArgeting Chimeras (PROTACs)

Answer 7

• addition of a molecule that will recruit ubiquition ligase (E3) and bring it to the target protein
• detaches once the target is polyubiquinated
• contains 2 molecules that are linked with a linker

Question 8

POI ligand

Answer 8

PROTAC molecule that attaches to the target protein

Question 9

E3 ligase ligand

Answer 9

PROTAC molecule that attaches to the E3 ligase

Question 10

installation of analogs of PTMs

Answer 10

• chemically controlled, therefore the amount of methylation is chosen
• Cys can be converted to dehydroalanine (Dha) to make it a good electrophile

Question 11

Dha site-directed mutagenesis

Answer 11

• multiple sites of kinase can be phosphorylated, therefore active site that is crucial is unknown
• test both active sites by attaching one Dha per experiment and seeing its effect biological effect