Conformational changes cooperative

Protein kinases, in cooperation with other proteins, form multiprotein complexes which are susceptible to activation upon external agonist stimuli. According to different functions in cell-cycle regulation, the conformational changes are initiated by autophosphorylation and dimerization transmitted by the previously discussed second messengers cAMP, cGMP, IP3, PIP3, AA and DAG. 

Figure 11. Allosteric regulation A conformational change of the active site of an enzyme induced by reversible binding of an effector molecule (A). The model of Monod, Wyman, and Changeux (B) Cooperativity in the MWC is induced by a shift of the equilibrium between the T and R state upon binding of the receptor. Note that the sequential dissociation constants Kr and KR do not change. The T and R states of the enzyme differ in their catalytic properties for substrates. Both plots are adapted from Ref. 140. See color insert.

We have already discussed the physical reason for the effect of the parameters h and K on the indirect correlation (Section 4.5) or, equivalently, on the induced conformational changes. But we still need an intuitive explanation of the effect of q. Why does q = 1 mean no communication between the sites Why does q < 1 result in positive indirect cooperativity or, equivalently, induces conformational change in the second subunit in the same direction as in the first subunit And why does q > 1 have the opposite effect ... 

As we have seen in the previous subsection, this reversal of the induced conformational changes, when q > 1, is also responsible for the change in the sign of the indirect cooperativity. 

Binding of O2 to one of the subunits of the T form leads to a local conformational change that weakens the association between the subunits. Increasing O2 partial pressure thus means that more and more molecules convert to the higher-af nity R form. This cooperative interaction between the subunits increases the O2 af nity of Hb with increasing O2 concentrations—i. e., the O2 saturation curve is sigmoidal (see p. 282). 

Enzyme active sites and receptors rarely interact with hgands without some attendant change in conformation, and the ability to detect and quantify a conformational change hes at the heart of contemporary biochemical kinetics. See Induced Fit Model Fluorescence Spectroscopy Linked Functions Flemoglobin Cooperativity... 

Slow transitions produced by enzyme isomerizations. This behavior can lead to a type of cooperativity that is generally associated with ligand-induced conformational changes . A number of enzymes are also known to undergo slow oligomerization reactions, and these enzymes may display unusual kinetic properties. If this is observed, it is advisable to determine the time course of enzyme activation or inactivation following enzyme dilution. See Cooperativity Bifurcation Theory Lag Time... 

---