R-and T-states

CPR can be used to find continuous paths for complex transitions that might have hundreds of saddle points and need to be described by thousands of path points. Examples of such transitions include the quaternary transition between the R and T states of hemoglobin [57] and the reorganization of the retinoic acid receptor upon substrate entry [58]. Because CPR yields the exact saddle points as part of the path, it can also be used in conjunction with nonnal mode analysis to estimate the vibrational entropy of activation... 

Effector molecules switch allosteric proteins between R and T states... 

The two states have the same affinity for ATP but differ with respect to their affinity for the substrate F6P, the allosteric effector ADP and the inhibitor PEP. Because of these differences in affinity, ligand binding can shift the equilibrium between the R and T states to favor one or the other state depending on which ligand is bound. 

In 1965, Jacques Monod, Jeffries Wyman, and Jean-Pierre Changeux proposed a theoretical model of allosteric transitions based on the observation that allosteric proteins are oligomers. They suggested that allosteric proteins can exist in (at least) two conformational states, designated R, signifying relaxed, and T, or taut, and that, in each protein molecule, all of the subunits have the same conformation (either R or T). That is, molecular symmetry is conserved. Molecules of mixed conformation (having subunits of both R and T states) are not allowed by this model. 

The results obtained by measuring the affinity to oxygen in the presence of various monohydric alcohols (methanol, ethanol, 2-propanol, 1-propanol) 140-144> were interpreted in terms of the Monod-Wyman-Changeux model145), by which the change of the standard free-energy difference between R and T state in the absence of oxygen, due to the addition of alcohol, can be determined, i.e. 

Unzai S et al Rate constants for O2 and CO binding to the alpha and beta subunits within the R and T states of human hemoglobin. J Biol Chem 1998 273 23150. 

Control in allosteric enzymes may take two extreme forms.4 In K (= binding) systems, the ones discussed so far, the substrate and the effector molecules have different affinities for the R and T states. The binding of an effector alters the affinity of the enzyme for the substrate, and vice versa. The R and the T states can have the same intrinsic value of cat, and activity is modulated by changes in affinity for the substrate. In V (= rate) systems, the substrate has the same affinity for both states, but one state has a much higher value of kCM. The effector molecule binds preferentially to one of the two states, and so modulates activity by changing the equilibrium position between the two. As the substrate binds... 

The transition between the R and T states also involves large changes in the conformation of the r subunits. These changes include both the peripheral domain where CTP or ATP binds and the domain that interfaces with the c subunits (see figs. 9.17 and 9.18). However, it still is not clear how the binding of CTP to the peripheral domain tips the conformational equilibrium in favor of T, whereas ATP,... 

Comparisons between R- and T-state hemoglobins on the one hand and a variety of synthetic model compounds on the other have allowed an evaluation of the possible occurrence and importance of electronic, proximal-base tension, and distal-side steric effects on the kinetics of ligation of CO and 02. Although all of these effects could influence the reactivities of hemoproteins, we conclude that hemoglobin reactivity and cooperativity are controlled predominantly by the presence or absence of proximal-base tension. 

Aime, S., Ascenzi, R, Comoglio, E., et al. (1995) Molecular recognition of R- and T-states of human adult hemoglobin by a paramagnetic Gd(II 1) complex by means of the measurement of solvent water proton relaxation rate. Journal of the American Chemical Society, 117, 9365-9366. 

B. There are equal concentrations of the R and T states of the allosteric protein. 

The binding of O2 to hemoglobin can be mathematically explained by both the MWC and KNF/DE models. Given the crystallographic snapshots of the R and T states and abundant biochemical data, which model best explains the cooperativity in Hb Both. 

The MWC two-state model for cooperative ligand binding (A) Free-energy relationships among R and T states (B) Calculation of the allosteric constants from the binding curve. 

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