モノー・ワイマン・シャンジューモデル、Monod-Wyman-Changeuxモデル

WordNet

display (clothes) as a mannequin; "model the latest fashion"
the act of representing something (usually on a smaller scale) (同)modelling, modeling
representation of something (sometimes on a smaller scale) (同)simulation
a representative form or pattern; "I profited from his example" (同)example
a person who poses for a photographer or painter or sculptor; "the president didnt have time to be a model so the artist worked from photos" (同)poser
someone worthy of imitation; "every child needs a role model" (同)role model
a hypothetical description of a complex entity or process; "the computer program was based on a model of the circulatory and respiratory systems" (同)theoretical account, framework
a type of product; "his car was an old model"
construct a model of; "model an airplane" (同)mock up
form in clay, wax, etc; "model a head with clay" (同)mold, mould
plan or create according to a model or models (同)pattern
assume a posture as for artistic purposes; "We dont know the woman who posed for Leonardo so often" (同)pose, sit, posture
create a representation or model of; "The pilots are trained in conditions simulating high-altitude flights" (同)simulate
a particular functioning condition or arrangement; "switched from keyboard to voice mode"
the most frequent value of a random variable (同)modal value
any of various fixed orders of the various diatonic notes within an octave (同)musical mode
relating to a recently developed fashion or style; "their offices are in a modern skyscraper"; "tables in modernistic designs"; (同)modern, modernistic
a British teenager or young adult in the 1960s; noted for their clothes consciousness and opposition to the rockers
resembling sculpture; "her finely modeled features"; "rendered with...vivid sculptural effect"; "the sculpturesque beauty of the athletes bodies" (同)sculptural, sculptured, sculpturesque
French biochemist who (with Francois Jacob) explained how genes are activated and suggested the existence of messenger RNA (1910-1976) (同)Jacques Monod, Jacques Lucien Monod

PrepTutorEJDIC

(通名縮小した)(…の)『模型』,ひな型《+『of』+『名』》 / 《単数形で》(…の)『模範』,手本《+『of』+(『for』)+『名』》 / (美術家・作家などの)モデル,ファッションモデル / (自動車・服装などの)型,式《+『of』+『名』》 / 《英》《単数形で》(…と)そっくりな人(物),(…の)生き写し《+『of』+『名』》 / 『模型の』,見本の / 『日範的な』,申し分のない / (ある材料で)…‘の'模型を作る,‘を'型どる《+『名』+『in』+『名』〈材料〉》 / (手本・型に合わせて)…‘を'作る《+『名』+『after』(『on, upon』)+『名』(a person's do『ing』)》 / 〈洋装・髪型などの〉‘の'モデルをする / (…で)(原型)を作る《+『in』+『名』》 / (ファッションショーなどで)モデルをする
〈C〉(…の)『方法』,やり方,流儀《+『of』+『名』(do『ing』)》 / 〈U〉〈C〉(服装などの)『流行』,モード / 〈C〉(動詞の)法,叙法(mood) / 音階(scale)
モッズふうな(服装・音楽などについて伝統にとらわれない考え方の一つ)[modernの短縮形]

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/12/10 08:59:43」(JST)

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An allosteric transition of a protein between R and T states, stabilised by an Agonist, and Inhibitor and a Substrate.

In biochemistry, the Monod-Wyman-Changeux model (MWC model, also known as the concerted model or symmetry model) describes allosteric transitions of proteins made up of identical subunits. It was proposed by Jean-Pierre Changeux based on his PhD experiments, and described by Jacques Monod, Jeffries Wyman, and Jean-Pierre Changeux. It stands in opposition to the sequential model.

The concept of two distinct symmetric states is the central postulate of the MWC model.The main idea of the model is that regulated proteins, such as many enzymes and receptors, exist in different interconvertible states in the absence of any regulator. The ratio of the different conformational states is determined by thermal equilibrium. This model, alternatively termed the MWC model, is defined by the following rules:

An allosteric protein is an oligomer of protomers that are symmetrically related (for hemoglobin, we shall assume, for the sake of algebraic simplicity, that all four subunits are functionally identical).
Each protomer can exist in (at least) two conformational states, designated T and R; these states are in equilibrium whether or not ligand is bound to the oligomer.
The ligand can bind to a protomer in either conformation. Only the conformational change alters the affinity of a protomer for the ligand. The regulators merely shift the equilibrium toward one state or another. For instance, an agonist will stabilize the active form of a pharmacological receptor. Phenomenologically, it looks as if the agonist provokes the conformational transition. One crucial feature of the model is the dissociation between the binding function (the fraction of protein bound to the regulator), and the state function (the fraction of protein under the activated state), cf below. In the models said of "induced-fit", those functions are identical.

In the historical model, each allosteric unit, called a protomer (generally assumed to be a subunit), can exist in two different conformational states - designated 'R' (for relaxed) or 'T' (for tense) states. In any one molecule, all protomers must be in the same state. That is to say, all subunits must be in either the R or the T state. Proteins with subunits in different states are not allowed by this model. The R state has a higher affinity for the ligand than the T state. Because of that, although the ligand may bind to the subunit when it is in either state, the binding of a ligand will increase the equilibrium in favor of the R state.

Two equations can be derived, that express the fractional occupancy of the ligand binding site (Y) and the fraction of the proteins in the R state (R):

Where is the allosteric constant, that is the ratio of proteins in the T and R states in the absence of ligand, is the ratio of the affinities of R and T states for the ligand, and , the normalised concentration of ligand.

This model explains sigmoidal binding properties as change in concentration of ligand over a small range will lead to a vast increase in the proportion of molecules in the R state, and thus will lead to a high association of the ligand to the protein.

The MWC model proved very popular in enzymology, and pharmacology, although it has been shown inappropriate in a certain number of cases. The best example of a successful application of the model is the regulation of hemoglobin function. Extension of the model have been proposed for lattices of proteins, for instance by Changeux, Thiery, Tung and Kittel, by Wyman or by Duke, Le Novere and Bray.

References

Changeux J.-P. (1964). Allosteric interactions interpreted in terms of quaternary structure. Brookhaven Symposia in Biology, 17: 232-249.
Monod J., Wyman J., and Changeux J.-P. (1965). On the nature of allosteric transitions: a plausible model. J. Mol. Biol. 12: 88-118.
Changeux J.-P., Thiery J., Tung Y., Kittel C. (1967). On the cooperativity of biological membranes. PNAS 57: 335-341
Wyman J (1969). Possible allosteric effects in extended biological systems. J. Mol Biol. 14:523-538.
Edelstein SJ (1971). Extensions of the allosteric model for haemoglobin. Nature. 230:224-227.
Changeux JP, Edelstein SJ (1998). Allosteric receptors after 30 years. Neuron 21: 959-980.
Duke TA, Le Novere N, Bray D (2001). Conformational spread in a ring of proteins: a stochastic approach to allostery. J. Mol Biol. 308:541-553.
Changeux JP, Edelstein SJ. (2005) Allosteric mechanisms of signal transduction. Science, 2005 Jun 3;308(5727):1424-8.

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English Journal

Disruption of the Na+ ion binding site as a mechanism for positive allosteric modulation of the mu-opioid receptor.

Livingston KE1, Traynor JR2.
Proceedings of the National Academy of Sciences of the United States of America.Proc Natl Acad Sci U S A.2014 Dec 23;111(51):18369-74. doi: 10.1073/pnas.1415013111. Epub 2014 Dec 8.
Positive allosteric modulation of the mu-opioid receptor (MOPr), the site of action of all clinically used opioids, represents a potential approach for the management of pain. We recently reported on positive allosteric modulators of MOPr (mu-PAMs), a class A G protein coupled receptor (GPCR). This
PMID 25489080

A conformation-equilibrium model captures ligand-ligand interactions and ligand-biased signalling by G-protein coupled receptors.

Roth S1, Bruggeman FJ.
The FEBS journal.FEBS J.2014 Oct;281(20):4659-71. doi: 10.1111/febs.12970. Epub 2014 Sep 17.
G-protein coupled receptors (GPCRs) are a versatile, important class of cell-surface receptors. GPCRs occur in different conformations that exist in a dynamic ligand-sensitive equilibrium. These conformations vary in their affinities for intracellular signalling proteins and initiate signalling via
PMID 25145284

Incorporating covalent and allosteric effects into rate equations: the case of muscle glycogen synthase.

Palm DC1, Rohwer JM1, Hofmeyr JH.
The Biochemical journal.Biochem J.2014 Sep 15;462(3):525-37. doi: 10.1042/BJ20140196.
Several enzymes have been described that undergo both allosteric and covalent regulation, but, to date, there exists no succinct kinetic description that is able to account for both of these mechanisms of regulation. Muscle glycogen synthase, an enzyme implicated in the pathogenesis of several metab
PMID 24969542

Japanese Journal

カルシウムイオン受容体挙動のアロステリックモデルによる線形システム解析

田村博司,平山博史,西村敏博,福山裕三
電子情報通信学会技術研究報告. MBE, MEとバイオサイバネティックス 96(113), 59-66, 1996-06-20
… カルシウムチャンネル活性化における受容体の構造変化はMonod-Wyman-Changeux型アッロステリックモデルにより表現した。 …
NAID 110003286970

The calculation of the Interaction Energy Between Subunits of Hemoglobin molecule

Arata Yasuhide,新田保秀
琉球大学教育学部紀要第二部 (19), 93-111, 1976-03
… This substantiates Perutz' model energetically, and give some quide to Monod-Wyman-Changeux's model. …
NAID 120001871629