Cooperativity: a unified view

Acerenza, Luis; Mizraji, Eduardo

doi:10.1016/s0167-4838(96)00228-2

Cited by 39 publications

(38 citation statements)

References 18 publications

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“…In the same contribution, it was also shown that a similar decomposition could be applied for arbitrary equilibrium binding systems, provided that there is a one-to-one relationship between free and occupied sites. In this case, the average is taken over the elementary equilibrium constants of the sites (microscopic decomposition) [17]. In the present paper, it is shown that these two types of decompositions (stoichiometric and microscopic) are particular cases of a more general pseudo-linear decomposition of the global affinity.…”

Section: Introductionmentioning

confidence: 77%

“…Notice that K c is, in general, a function of the ligand concentration and thus cannot, a priori, be regarded as an equilibrium constant, as defined in the standard chemical thermodynamics. However, it was stated in a previous contribution [17] that when a system can be represented by an Adair equation (4), the global association quotient (1) can be decomposed in terms of…”

Section: Decomposition Of the Global Association Quotient For Adair Bmentioning

confidence: 99%

“…The present article is centred in the investigation of the properties of an experimental parameter that allows a highly sensitive measure of the cooperative behaviour of macromolecular binding systems [11,[16][17][18]. This parameter, which we have called "global association quotient", is directly related to the Hill number and has a cardinal property: It presents a simple inner structure related to the binding properties of the subsystems that are responsible for the observed cooperative behaviour, making its interpretation transparent [17].…”

Section: Introductionmentioning

confidence: 99%

“…This parameter, which we have called "global association quotient", is directly related to the Hill number and has a cardinal property: It presents a simple inner structure related to the binding properties of the subsystems that are responsible for the observed cooperative behaviour, making its interpretation transparent [17].…”

Section: Introductionmentioning

confidence: 99%

“…The global association quotient (also called average equilibrium function [18], affinity function [10], global equilibrium quotient [17] or apparent equilibrium constant [11]) is defined by:…”

Section: Introductionmentioning

confidence: 99%

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A Hierarchical Approach to Cooperativity in Macromolecular and Self-Assembling Binding Systems

et al. 2008

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The study of complex macromolecular binding systems reveals that a high number of states and processes are involved in their mechanism of action, as has become more apparent with the sophistication of the experimental techniques used. The resulting information is often difficult to interpret because of the complexity of the scheme (large size and profuse interactions, including cooperative and self-assembling interactions) and the lack of transparency that this complexity introduces into the interpretation of the indexes traditionally used to describe the binding properties. In particular, cooperative behaviour can be attributed to very different causes, such as direct chemical modification of the binding sites, conformational changes in the whole structure of the macromolecule, aggregation processes between different subunits, etc. In this paper, we propose a novel approach for the analysis of the binding properties of complex macromolecular and self-assembling systems. previous work, it was shown that K c could be decomposed as an average of equilibrium constants in two ways: intrinsic constants for Adair binding systems and elementary constants for the general case. In this study, we show that these two decompositions are particular cases of a more general expression, where the average is over partial association quotients, associated with subsystems from which the system is composed. We also show that if the system is split into different subsystems according to a binding hierarchy that starts from the lower, microscopic level and ends at the higher, aggregation level, the global association quotient can be decomposed following the hierarchical levels of macromolecular organisation. In this process, the partial association quotients of one level are expressed, in a recursive way, as a function of the partial quotients of the level that is immediately below, until the microscopic level is reached. As a result, the binding properties of very complex macromolecular systems can be analysed in detail, making the mechanistic explanation of their behaviour transparent. In addition, our approach provides a modelindependent interpretation of the intrinsic equilibrium constants in terms of the elementary ones.

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Section: Introductionmentioning

confidence: 77%

Section: Decomposition Of the Global Association Quotient For Adair Bmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Hierarchical Approach to Cooperativity in Macromolecular and Self-Assembling Binding Systems

et al. 2008

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Allosterism and Drug Discovery

Bell

2021

Burger's Medicinal Chemistry and Drug Discovery

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Interest in allostery and drug development has significantly expanded with increasingly broad ranges of targets and diseases. Experimental and computational approaches have led to advances in understanding of the mechanisms and roles of protein dynamics and conformational states, and come together in the concept of conformational selection. The models of Monod, Wyman, and Changeux and Koshland, Nemethy, and Filmer provide conceptual explanations of homotropic cooperativity and heterotropic allostery, while conformational selection provides realistic detail that can be exploited in drug design. Distinction between allostery and cooperativity and development of approaches to identify cryptic sites on proteins significantly expands the range of targets for allosteric drug design. High‐throughput screening and SAR optimization remain a staple of drug design, however, increased understanding of the thermodynamics of protein–ligand interactions and conformational changes, and the mechanisms of information flow between existing allosteric sites and across subunit interfaces or between allosteric and active sites, rational design of ligands to interact with a cryptic “allosteric” site on any protein becomes possible. Recent “omics” approaches to identify druggable targets both genome wide and in vivo further enhance the range of targets for drug design, both covalent and noncovalent, exploiting allosteric and cooperative properties of proteins.

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Positive feedback in cellular control systems

Mitrophanov¹,

Groisman²

2008

BioEssays

256

240

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Feedback loops have been identified in a variety of regulatory systems and organisms. While feedback loops of the same type (negative or positive) tend to have properties in common, they can play distinctively diverse roles in different regulatory systems, where they can affect virulence in a pathogenic bacterium, maturation patterns of vertebrate oocytes and transitions through cell cycle phases in eukaryotic cells. This review focuses on the properties and functions of positive feedback in biological systems, including bistability, hysteresis and activation surges.

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Cooperativity: a unified view

Cited by 39 publications

References 18 publications

A Hierarchical Approach to Cooperativity in Macromolecular and Self-Assembling Binding Systems

A Hierarchical Approach to Cooperativity in Macromolecular and Self-Assembling Binding Systems

Allosterism and Drug Discovery

Positive feedback in cellular control systems

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