Mechanism of allostery

As the mechanism of allostery became the main focus of Lipscomb s interests in protein structure and fimction in the 1990s, again the con arative approach was brought to bear on the problem. The remarkable fact, first demonstrated in the case of hemoglobin (initially by Felix Haurowitz and ultimately in detail by Max Perutz), that allosteric enzymes underwent a dramatic... 

This study and its predecessors have made at least modest inroads into the largely uncharted territory of the intricate interplay between static interactions and their dynamics in determining the stability of biologically active complexes. They have also raised a host of new questions, which remain to be answered before we could claim to understand the mechanisms of allostery and induced fit. Massive collection of data will be necessary to achieve this end. A correlation between the affinity (thermodynamic stability) and dynamic stability of a complex remains to be established - whether one considers intramolecular -intra- and interchain - complexes that hold the protein together, or the intermolecular complexes of a protein with its ligands. The atomic motions reflected in such processes as nuclear relaxation and backbone proton exchange -the main NMR indicators of protein dynamics remain to be described. Last, not... 

One of the most important mechanisms for regulating protein function entails allostery. Broadly speaking, allostery refers to any change in a protein s tertiary or quaternary structure or both induced by the binding of a ligand, which may be an activator, inhibitor, substrate, or all three. Allosteric regulation is particularly prevalent in multlmerlc enzymes and other proteins. We first explore several ways in which allostery influences protein function and then consider other mechanisms for regulating proteins. 

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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