Monod-Wyman-Changeux

FIGURE 15.9 Monod-Wyman-Changeux (MWC) model for allosteric transitions. Consider a dimeric protein that can exist in either of two conformational states, R or T. Each subunit in the dimer has a binding site for substrate S and an allosteric effector site, F. The promoters are symmetrically related to one another in the protein, and symmetry is conserved regardless of the conformational state of the protein. The different states of the protein, with or without bound ligand, are linked to one another through the various equilibria. Thus, the relative population of protein molecules in the R or T state is a function of these equilibria and the concentration of the various ligands, substrate (S), and effectors (which bind at f- or Fj ). As [S] is increased, the T/R equilibrium shifts in favor of an increased proportion of R-conformers in the total population (that is, more protein molecules in the R conformational state). 

Glycogen phosphorylase conforms to the Monod-Wyman-Changeux model of allosteric transitions, with the active form of the enzyme designated the R state and the inactive form denoted as the T state (Figure 15.17). Thus, AMP promotes the conversion to the active R state, whereas ATP, glucose-6-P, and caffeine favor conversion to the inactive T state. 

First draw both Lineweaver-Burk plots and Hanes-Woolf plots for the following a Monod-Wyman-Changeux allosteric K enzyme system, showing separate curves for the kinetic response in (1) the absence of any effectors (2) the presence of allosteric activator A and (3) the presence of allosteric inhibitor I. Then draw a similar set of curves for a Monod-Wyman-Changeux allosteric Uenzyme system. 

In the Monod-Wyman-Changeux model for allosteric regulation, what values of L and relative affinities of R and T for A will lead activator A to exhibit positive homotropic effects (That is, under what conditions will the binding of A enhance further A-binding, in the same manner that S-binding shows positive coop-... 

Because this enzyme catalyzes the committed step in fatty acid biosynthesis, it is carefully regulated. Palmitoyl-CoA, the final product of fatty acid biosynthesis, shifts the equilibrium toward the inactive protomers, whereas citrate, an important allosteric activator of this enzyme, shifts the equilibrium toward the active polymeric form of the enzyme. Acetyl-CoA carboxylase shows the kinetic behavior of a Monod-Wyman-Changeux V-system allosteric enzyme (Chapter 15). 

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. 

I am surely not going to describe all of these complicated discussions which took place after the famous Monod-Wyman-Changeux paper, with the result that an increasing number of molecular states were introduced and that both kinds of processes, the induced-fit one, the concerted or... 

Linked-function mechanisms for cooperative binding interaction of metabolites and/or drugs, based on the presence of two or more different conformational states of the protein or receptor. See Adair Equation Cooperative Ligand Binding Hemoglobin Hill Equation Plot Koshland-Nemethy-Filmer Model Monod-Wyman-Changeux Model Negative Cooperativity Positive Cooperativity... 

In the context of the Monod-Wyman-Changeux concerted-transition model for allosteric effects, one usually considers the effects of specific site occupancy on the behavior of other binding sites. Thus, a more correct... 

A graphical procedure used to determine, in cooperative systems, values for L (the ratio of the T to R state in the absence of any binding ligand in the Monod-Wyman-Changeux model) and n (the stoichiometry of binding) in exclusive binding systems (c = 0 where c = i.e., the ratio of the intrinsic dissociation constants for... 

Scatchard plots for ligand saturation behavior of an oligomeric protein exhibiting positive cooperativity, negative cooperativity, or independent binding behavior. For addition details, See Monod-Wyman-Changeux Cooperativity Model Scatchard Plot... 

A subset in allosteric models of cooperativity. If an allosteric effector, upon binding to a cooperative enzyme, alters the Michaelis or dissociation constants (or [S0.5] value) for the substrate(s) (but not the h"max values), then that protein is a A system enzyme. See Monod-Wyman-Changeux Model K. E. Meet (1980) Meth. Enzymol. 64, 139. 

Note that negative cooperativity cannot occur in the Monod-Wyman-Changeux allosteric transition model, because the dissociation constant is equivalent for all sites. Thus, positive cooperativity can only result in this binding mechanism as a consequence of the recruitment of binding sites from the T-state in an all-or-none transition to the R-state. Any occurrence of negative cooperativity can be regarded as prima facie evidence... 

It should also be noted that the common models of allosterism (e.g., the Monod-Wyman-Changeux model and the Koshland-Nemethy-Filmer model) assume rapid equilibrium binding. 

Reduced concentrations are also useful in the Monod-Wyman-Changeux cooperativity model, where a = [F]/ Kj and ca = [F]/X t. This makes polynomial functions simpler to handle. For example, if ligand F binds exclusively to the R-state, then the ligand F saturation function, Tf, for an n-site protein equals (1 + +... 

MICHAELIS-MENTEN EQUATION MICHAELIS-MENTEN KINETICS MONOD-WYMAN-CHANGEUX MODEL NEGATIVE COOPERATIVITY POSITIVE COOPERATIVITY Cooperativity index. 

MONOD-WYMAN-CHANGEUX MODEL COORDINATE-COVALENT BOND COORDINATION NUCLEARITY... 

STEREOCHEMICAL TERMINOLOGY, lUPAC RECOMMENDATIONS HETEROTROPIC EFFECT MONOD-WYMAN-CHANGEUX MODEL HEMOGLOBIN ALLOSTERISM... 

COOPERATIVITY ALLOSTERISM INDUCED FIT MODEL MONOD-WYMAN-CHANGEUX MODEL INDEPENDENT BINDING LINKED FUNCTIONS ADAIR EQUATION POSITIVE COOPERATIVITY NEGATIVE COOPERATIVITY KOSMOTROPES CHAOTROPIC AGENTS HOFMEISTER SERIES Kp, Kq, K .. . ... 

MONOD-WYMAN-CHANGEUX MODEL Ligand binding sites,... 

MONOD-WYMAN-CHANGEUX MODEL MONOGLYCERIDE LIPASE MONO-ISO MECHANISMS... 

EXPONENTIAL BREAKDOWN SYMBOLIC COMPUTING Symmetry-conserving allosteric model, MONOD-WYMAN-CHANGEUX MODEL SYMPORT Symproportionation,... 

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