Kinases

Question 1

phosphorylation

Answer 1

phosphate added to -OH of serine, threonine and tyrosine. Necleophilically attacks gamma phosphate of ATP. Regulates protein ativity

Question 2

secondary protein modifications

Answer 2

Acetylation, glycosylation, ubiquitination

Question 3

structure of ATP

Answer 3

ribose sugar, adenine at C1’, alpha beta and gamma (phosphoanhydride bonds) phosphates at C5’

Question 4

classification of protein kinases

Answer 4

kinases are classified by the AA phosphorylated (tyr kinase), their substrate myosin light chain kinase MLCK), their activation (mitogen activated protein kinase MAPK), or their phylogenetic relationship

Question 5

structure/function of protein kinases

Answer 5

small and large lobe, ATP binds between clefts of lobes, substrate interaction on large lobe. Closed conformation of glycine rich loop forces gamma phosphate of ATP into right position for phosphorylation. Open conformation of glycine rich loop allows PO4 exchane and generates ADP

Question 6

principles of regulation

Answer 6

active conformation of all kinases is well conserved (makes specific inhibitors for kinases difficult). Inactive form is not. ATP binding pocket is somehow distorted in inactive conformation. Many kinases activation loop has to be phosphorylated for full activity. Another common regulation block active sire with inhibitory pseudo-substrate sequence.