BIOC 3560 Lecture 11: biochem PACK ELEVEN.pdf
3 Dec 2014
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Mechanisms of enzyme regulation: allostery, reversible, covalent modification, interaction with regulatory proteins, proteolytic cleavage. Regulation of the eukarotic cell cycle by protein kinases. Cyclin-dependent kinases regulate passage through the cell cycle. Complex regulation: binding of cyclin, phosphorylation/dephosphorylation of cdk, binding of cdk inhibitors (e. g. p21, synthesis/degradation of cdks and cyclins. Compare the relative position of the t loop in this figure and the next one (which has cyclin bound). 12-45 cyclin binding opens up the active site of cdk. Conformational changes in cdk activation: cyclin-controlled, pstaire helix moves into catalytic cleft. Glu51 involved in catalysis: t loop changes conformation and position, allows access to catalytic cleft, exposes threonine (thr160) on t loop. Conformational changes in cdk activation: phosphorylation-controlled, dephosphorylation of tyr15 allows access for atp, phosphorylation of thr160. E. g. by cdk-activating kinase (cak: t loop forced out of catalytic cleft, thr160-po4 binds 3 arg side-chains (including arg50, stabilizes active conformation (r state)
