Model of Koshland. Nemethy and Filmer

An Alternative Allosteric Model The Sequential Allosteric Model of Koshland, Nemethy, and Filmer... 

The sequential model of Koshland, Nemethy and Filmer (Koshland et al., 1966). The sequential model proposes that the conformational stability of each subunit is determined by the conformations of the subunits with which it is in contact. The model is based on three postulates ... 

Two main models, the concerted (or symmetry) model of Monod, Wyman and Changeux (MWC) and the sequential model of Koshland, Nemethy and Filmer (KNF), form the basis of approaches to explain the sigmoidal relationship between and [S] (Figure 6.11) in molecular terms. Although... 

The second extreme case, suggested by Koshland, Nemethy, and Filmer (KNF) (Koshland et al., 1966), is also known as the sequential model. The mathematical conditions required to obtain this limiting case are quite severe. First, it is assumed that, in the absence of a ligand, one of the conformations is dominant, say the LL form. In addition, it is assumed that a ligand binding to any subunit will change the conformation of that subunit into the H form. These assumptions lead to the consideration of only the four diagonal states of Fig. 4.18, for which the PF is... 

In 1966, Koshland, Nemethy, and Filmer described several models for oligomeric proteins or enzymes with different permissible site-site interactions (Koshland et al, 1966). The KNF models avoid the assumption of symmetry of the MWC model, but use another simplifying features. They assume that the progress fromT to the ligand-bound R state is a sequential process. The conformation of each subunit changes in turn as it binds the ligand, and there is no dramatic switch from... 

Koshland, D. E., Jr., Nemethy, G., and Filmer, D., 1966. Compari.son of experimental binding data and dieoretical models in proteins containing snbnnits. Biochemistry 5 365-385. The KNF model. 

D. E. Koshland, G. Nemethy, and D. Filmer, Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry 5(1), 365 368 (1966). 

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... 

A model used to explain cooperativity on the basis of ligand-induced changes in conformation that may or may not alter the subunit-subunit interfaces of oligomeric enzymes and receptors. This model has also been referred to as the Adair-Koshland-Nemethy-Filmer model (AKNF model), the induced-fit model, and the sequential model. 

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. 

Koshland-Nemethy-Filmer/Dalziel-Engel The Sequential Model. A second model to describe cooperativity within systems was proposed independently by both the Koshland and Dalziel groups. Unlike the concerted model, the sequential model does not constrain the oligomer to either the T or R state and therefore no preequilibrium of states is present. The sequential model, also known as the induced-fit model, hypothesizes that when a ligand binds, a conformational change oc-... 

As discussed in Section 15.1, numerous protein systems have been observed to behave in a manner consistent with a structural-mechanical basis of allosteric control between coupled sites, in which the sites are connected structurally by a network of interactions or pathways [14,15]. In these systems, allostery typically has been presented in terms of the Monod-Wyman-Changeux (MWC) [8] and Koshland-Nemethy-Filmer (KNF) [9] models, both of which are special cases of a more general model [61]. Briefly, the MWC model describes allostery as originating from the equilibria between two macroscopic states, each of which can bind ligand with different affinities. In this model, the equilibrium is driven toward the high-affinity state by mass action. The KNF model, however, relies on an induced fit ... 

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