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Allosteric

The influence of solvent can be incorporated in an implicit fashion to yield so-called langevin modes. Although NMA has been applied to allosteric proteins previously, the predictive power of normal mode analysis is intrinsically limited to the regime of fast structural fluctuations. Slow conformational transitions are dominantly found in the regime of anharmonic protein motion. [Pg.72]

Antagonist An antagonist is a receptor ligand preventing the action of an agonist, in a direct (competitive) or indirect (allosteric) manner. [Pg.599]

Fig. 21. (a) Diagrammatical representation of an allosteric receptor mechanism (b) allosteric binding of a thymine derivative promoted on uptake (34). [Pg.186]

NMD A receptors are selectively activated by A/-methyl-D-aspartate (NMD A) (182). NMD A receptor activation also requires glycine or other co-agonist occupation of an allosteric site. NMDAR-1, -2A, -2B, -2C, and -2D are the five NMD A receptor subunits known. Two forms of NMDAR-1 are generated by alternative splicing. NMDAR-1 proteins form homomeric ionotropic receptors in expression systems and may do so m situ in the CNS. Functional responses, however, are markedly augmented by co-expression of a NMDAR-2 and NMDAR-1 subunits. The kinetic and pharmacological properties of the NMD A receptor are influenced by the particular subunit composition. [Pg.551]

The allosteric effect is seen in hemoglobin which can exist in two quaternary stmctural states oxygenated (R) or deoxygenated (T). The binding of one O2 or some other effector to one of the subunits stabilizes the R form as compared to the T form. Binding of a second and third O2 stabilizes it even further. [Pg.211]

Steitz, T.A., et al. High resolution x-ray structure of yeast hexokinase, an allosteric protein exhibiting a non-symmetric arrangement of subunits. [Pg.65]

Effector molecules switch allosteric proteins between R and T states... [Pg.113]

For many years hemoglobin was the only allosteric protein whose stereochemical mechanism was understood in detail. However, more recently detailed structural information has been obtained for both the R and the T states of several enzymes as well as one genetic repressor system, the trp-repressor, described in Chapter 8. We will here examine the structural differences between the R and the T states of a key enzyme in the glycolytic pathway, phosphofructokinase. [Pg.114]

Figure 6.24 The function of the enzyme phosphofructokinase. (a) Phosphofructokinase is a key enzyme in the gycolytic pathway, the breakdown of glucose to pyruvate. One of the end products in this pathway, phosphoenolpyruvate, is an allosteric feedback inhibitor to this enzyme and ADP is an activator, (b) Phosphofructokinase catalyzes the phosphorylation by ATP of fructose-6-phosphate to give fructose-1,6-bisphosphate. (c) Phosphoglycolate, which has a structure similar to phosphoenolpyruvate, is also an inhibitor of the enzyme. Figure 6.24 The function of the enzyme phosphofructokinase. (a) Phosphofructokinase is a key enzyme in the gycolytic pathway, the breakdown of glucose to pyruvate. One of the end products in this pathway, phosphoenolpyruvate, is an allosteric feedback inhibitor to this enzyme and ADP is an activator, (b) Phosphofructokinase catalyzes the phosphorylation by ATP of fructose-6-phosphate to give fructose-1,6-bisphosphate. (c) Phosphoglycolate, which has a structure similar to phosphoenolpyruvate, is also an inhibitor of the enzyme.
Because of the crucial role of this enzyme in one of the most important bicxrhemical pathways in the cell, its allosteric properties have been studied extensively in solution. Interpretation of these studies in terms of the theory of allosteric enzymes led Monod and coworkers to conclude that ... [Pg.115]

The two states have the same affinity for ATP but differ with respect to their affinity for the substrate F6P, the allosteric effector ADP and the inhibitor PEP. Because of these differences in affinity, ligand binding can shift the equilibrium between the R and T states to favor one or the other state depending on which ligand is bound. [Pg.115]

The group of Phil Evans, MRC Laboratory of Molecular Biology, Cambridge, UK, has determined x-ray structures of bacterial PFK both in the R and the T states. These studies have confirmed the above conclusions and given insight into how an allosteric enzyme accomplishes its complex behavior. [Pg.115]

The basic kinetic properties of this allosteric enzyme are clearly explained by combining Monod s theory and these structural results. The tetrameric enzyme exists in equilibrium between a catalytically active R state and an inactive T state. There is a difference in the tertiary structure of the subunits in these two states, which is closely linked to a difference in the quaternary structure of the molecule. The substrate F6P binds preferentially to the R state, thereby shifting the equilibrium to that state. Since the mechanism is concerted, binding of one F6P to the first subunit provides an additional three subunits in the R state, hence the cooperativity of F6P binding and catalysis. ATP binds to both states, so there is no shift in the equilibrium and hence there is no cooperativity of ATP binding. The inhibitor PEP preferentially binds to the effector binding site of molecules in the T state and as a result the equilibrium is shifted to the inactive state. By contrast the activator ADP preferentially binds to the effector site of molecules in the R state and as a result shifts the equilibrium to the R state with its four available, catalytically competent, active sites per molecule. [Pg.117]

Perutz, M. Mechanisms of cooperativity and allosteric regulation in proteins. Cambridge Cambridge University Press, 1990. [Pg.119]

Schirmer, T., Evans, P.R. Structural basis of the allosteric behaviour of phosphofructokinase. Nature 343 140-145, 1990. [Pg.119]

Many biochemical and biophysical studies of CAP-DNA complexes in solution have demonstrated that CAP induces a sharp bend in DNA upon binding. This was confirmed when the group of Thomas Steitz at Yale University determined the crystal structure of cyclic AMP-DNA complex to 3 A resolution. The CAP molecule comprises two identical polypeptide chains of 209 amino acid residues (Figure 8.24). Each chain is folded into two domains that have separate functions (Figure 8.24b). The larger N-terminal domain binds the allosteric effector molecule, cyclic AMP, and provides all the subunit interactions that form the dimer. The C-terminal domain contains the helix-tum-helix motif that binds DNA. [Pg.146]

Some of the procaryotic DNA-binding proteins are activated by the binding of an allosteric effector molecule. This event changes the conformation of the dimeric protein, causing the helix-tum-helix motifs to move so that they are 34 A apart and able to bind to the major groove. The dimeric repressor for purine biosynthesis, PurR, induces a sharp bend in DNA upon binding caused by insertion of a helices in the minor groove between the two... [Pg.147]


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A Cyclic Model for Allosteric Regulatory Enzymes

A Simple Allosteric Regulation

AMPA receptors allosteric modulators

Allosteric Effects, A Big Surprise

Allosteric PRPP synthetase

Allosteric activation

Allosteric activation, of enzymes

Allosteric activators

Allosteric activators, glucokinase

Allosteric antagonism

Allosteric behavior

Allosteric binding

Allosteric binding sites

Allosteric binding, drug interactions

Allosteric cavity

Allosteric changes

Allosteric coefficient

Allosteric concept

Allosteric constant

Allosteric control

Allosteric control Monod-Wyman-Changeux model

Allosteric control effects

Allosteric control of enzymes

Allosteric control of repressor protein

Allosteric effect

Allosteric effect concerted model

Allosteric effect sequential model

Allosteric effect theoretical models

Allosteric effector site

Allosteric effectors

Allosteric effectors enzyme sensitivity

Allosteric effectors of hemoglobin

Allosteric effectors/modifiers

Allosteric effectors/modifiers negative

Allosteric effects hemoglobin

Allosteric effects in enzymes

Allosteric enhancers

Allosteric enzymes

Allosteric enzymes ATCase)

Allosteric enzymes Aspartate transcarbamoylase

Allosteric enzymes behavior

Allosteric enzymes catalytic

Allosteric enzymes concerted mechanism

Allosteric enzymes concerted model

Allosteric enzymes concerted-symmetry model

Allosteric enzymes heterotropic effects

Allosteric enzymes homotropic effects

Allosteric enzymes interaction

Allosteric enzymes negative allosterism

Allosteric enzymes phosphofructokinase 1 activation

Allosteric enzymes positive allosterism

Allosteric enzymes receptor tyrosine kinase

Allosteric enzymes regulatory

Allosteric enzymes sequential interaction model

Allosteric enzymes sequential model

Allosteric enzymes substrate binding

Allosteric enzymes subunits

Allosteric enzymes, inhibitor activator effect

Allosteric enzymes, protein-based

Allosteric equilibrium constant

Allosteric factors

Allosteric group

Allosteric indicator displacement

Allosteric inhibition

Allosteric inhibition of enzymes

Allosteric inhibitors

Allosteric interactions

Allosteric interactions feedback

Allosteric ligands

Allosteric mechanism

Allosteric model

Allosteric model for cAMP oscillations

Allosteric model for glycolytic oscillations

Allosteric modification

Allosteric modifiers

Allosteric modifiers, hemoglobin

Allosteric modulation

Allosteric modulator

Allosteric modulator examples

Allosteric modulator kinetics

Allosteric modulators

Allosteric phenomena

Allosteric phenomena activation

Allosteric pockets

Allosteric potentiating ligand

Allosteric properties

Allosteric properties of hemoglobin

Allosteric proteins

Allosteric proteins and

Allosteric proteins common features

Allosteric proteins hydrophobic association

Allosteric proteins theories

Allosteric reactions, glycolytic oscillations

Allosteric regulation

Allosteric regulation enzyme kinetics

Allosteric regulation equations

Allosteric regulation, reactivity

Allosteric regulation, structural

Allosteric regulation, structural basis

Allosteric regulators

Allosteric site

Allosteric sites, inhibitor selectivity

Allosteric theory

Allosteric transition

Allosteric transmission

Allosteric, defined

Allosteric, effectors enzymes

Allosteric, effectors equilibrium

Allosteric, effectors mechanisms

Allosteric, effectors models

Allosteric, effectors regulation

Allosteric/cooperative kinetics

Allosterically regulated enzyme

Allosterism

Allosterism

Allosterism and Cooperativity

Allosterism and Regulation

Allosterism concerted model

Allosterism glycogen metabolism

Allosterism haemoglobin

Allosterism interaction

Allosterism kinetics

Allosterism phosphofructokinase

Allosterism pyruvate dehydrogenase

Allosterism pyruvate kinase

Allosterism, binding

Alternative Theories on How Hemoglobins and Other Allosteric Proteins Work

Antagonism allosteric modulation

Antagonists allosteric

Apparent allosteric constant

Aspartate Carbamoyl Transferase Allosteric Control of Pyrimidine Biosynthesis

Aspartate transcarbamylase allosteric effectors

Benzodiazepines allosteric interactions with

Carbohydrate metabolism allosteric effects

Catalysis allosteric regulation

Catalysis and allosteric regulation

Concerted allosteric model

Conformation change allosteric phenomena

Cooperative Versus Allosteric Effects

Cooperative allosteric interactions

Cooperative phenomena allosteric

Cooperativity allosteric

Cooperativity allosteric proteins

Coupling allosteric

Diabetes allosteric activators

Dimers allosteric control

Displacement binding allosteric interaction

Displacement binding allosteric radioligands

Drug targets allosteric proteins

Efficient Guest-binding Achieved through Allosteric Effects

Enantioselective Inhibition and Activation Allosteric Effects

Enzyme activity allosteric regulation

Enzyme allosteric effects

Enzyme allosteric enzymes

Enzyme inhibitors allosteric

Enzyme regulation allosteric control

Enzyme regulation by allosteric effectors

Enzymes allosteric activation

Enzymes allosteric binding

Enzymes allosteric control

Enzymes allosteric regulation

Enzymes allosteric site

Enzymes allosteric systems

Enzymes, active conformation allosteric

Evolution allosteric proteins

Examples of Allosteric Proteins

GABA receptors partial allosteric modulators

GABAb allosteric modulators

Glucokinase allosteric

Glucose allosteric regulation

Glutamate receptors allosteric modulators

Glycogen Phosphorylase Combined Control by Allosteric Effectors and Phosphorylation

Glycogen phosphorylase allosteric control

Glycolysis Allosteric regulation

Hemoglobin Is an Allosteric Oxygen-Binding Protein

Hemoglobin allosteric change

Hemoglobin allosteric effector

Hemoglobin allosteric interactions

Hemoglobin allosteric modulator

Hemoglobin allosteric properties

Hemoglobin allosteric protein

Hemoglobin allosteric transition

Hemoglobin allosterism

Heterotropic allosteric effect

Heterotropic allosteric effectors

Heterotropic allosteric enzymes

Heterotropic allosteric interaction

Homotropic allosteric effect

Homotropic allosteric enzymes

Homotropic allosteric interaction

Inhibition allosteric stimulation

Inhibitors allosteric phenomena

Inhibitors allosteric site

Isozymes and Allosteric Enzymes

Kinase allosteric modulators

Kinetic binding allosteric modulators

Kinetics allosteric

Kinetics allosteric enzymes

Kinetics of Allosteric Proteins

Ligand binding allosteric sites

Mechanistic Descriptions of Allosteric Regulation

Metabolic control allosterism

Metabolic regulation allosteric enzymes

Metabolism allosteric interactions

Metabotropic allosteric modulator, positive

Michaelis allosterism

Michaelis-Menten kinetics, allosteric effect

Models of allosteric activity

Monod-Wyman-Changeux model of allosteric regulation

Muscle glycogen phosphorylase allosteric effectors

Necessity of amending the allosteric model for cAMP signalling

Negative allosteric effector

Negative allosteric modulation

Negative allosteric modulator

Negative allosterism

Non-competitive, reversible (allosteric) inhibitors

Nucleotide functions allosteric effects

Oxygen allosteric behavior

Phosphofructokinase allosteric effector regulation

Phosphofructokinase allosteric properties

Phosphofructokinase allosteric regulation

Phosphorylative allosteric

Phosphorylative allosteric transition

Physiology, question allosterism

Positive allosteric effector

Positive allosteric modulation

Positive allosteric modulator

Positive allosteric modulators

Positive allosterism

Positive heterotropic allosteric regulation

Positive homotropic system allosterism

Principal Features of Allosteric Regulation

Protein allosteric interactions

Pseudo-Allosteric Effect of Poly(L-lysine) Heme Complex

Pyruvate allosteric effectors

Receptor allosteric modulation

Receptor partial allosteric modulators

Receptor signaling allosteric effect

Receptor signaling allosteric modulators

Receptors allosteric site

Receptors allosteric theory

Ribonucleotide reductase allosteric regulation

Sigmoidal curves, allosteric

Sigmoidal curves, allosteric enzymes

Structure Basis of Allosteric Regulation Glycogen Phosphorylase

Structure allosteric

Subunit allosterism role

The Behavior of Allosteric Enzymes

The Concerted and Sequential Models for Allosteric Enzymes

The Symmetry Model Provides a Useful Framework for Relating Conformational Transitions to Allosteric Activation or Inhibition

Theoretical Models for Allosteric Effect

Transporter allosteric effect

Two Subunits Each Having One Site Allosteric Effect

Velocity allosteric effects

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