Allosteric site. Medical search

A site on an enzyme which upon binding of a modulator, causes the enzyme to undergo a conformational change that may alter its catalytic or binding properties.

The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.

The imide of phthalic acids.

A muscarinic antagonist used to study binding characteristics of muscarinic cholinergic receptors.

Cholinesterase reactivator occurring in two interchangeable isomeric forms, syn and anti.

A synthetic nondepolarizing blocking drug. The actions of gallamine triethiodide are similar to those of TUBOCURARINE, but this agent blocks the cardiac vagus and may cause sinus tachycardia and, occasionally, hypertension and increased cardiac output. It should be used cautiously in patients at risk from increased heart rate but may be preferred for patients with bradycardia. (From AMA Drug Evaluations Annual, 1992, p198)

A specific subtype of muscarinic receptor found in the lower BRAIN, the HEART and in SMOOTH MUSCLE-containing organs. Although present in smooth muscle the M2 muscarinic receptor appears not to be involved in contractile responses.

Allosteric enzymes that regulate glycolysis and gluconeogenesis. These enzymes catalyze phosphorylation of fructose-6-phosphate to either fructose-1,6-bisphosphate (PHOSPHOFRUCTOKINASE-1 reaction), or to fructose-2,6-bisphosphate (PHOSPHOFRUCTOKINASE-2 reaction).

Benzopyrroles with the nitrogen at the number two carbon, in contrast to INDOLES which have the nitrogen adjacent to the six-membered ring.

Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

A specific subtype of muscarinic receptor that has a high affinity for the drug PIRENZEPINE. It is found in the peripheral GANGLIA where it signals a variety of physiological functions such as GASTRIC ACID secretion and BRONCHOCONSTRICTION. This subtype of muscarinic receptor is also found in neuronal tissues including the CEREBRAL CORTEX and HIPPOCAMPUS where it mediates the process of MEMORY and LEARNING.

A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

The rate dynamics in chemical or physical systems.

A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)

Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).

An isoenzyme of GLYCOGEN PHOSPHORYLASE that catalyzes the degradation of GLYCOGEN in muscle. Mutation of the gene coding this enzyme is the cause of McArdle disease (GLYCOGEN STORAGE DISEASE TYPE V).

The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.

Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.

An enzyme that catalyzes the conversion of D-fructose 1,6-bisphosphate and water to D-fructose 6-phosphate and orthophosphate. EC 3.1.3.11.

Diphosphoric acid esters of fructose. The fructose-1,6- diphosphate isomer is most prevalent. It is an important intermediate in the glycolysis process.

The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)

The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.

The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).

CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.

The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.

Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.

A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in vascular tissue and plays an important role in regulating VASCULAR SMOOTH MUSCLE contraction.

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

Large collections of small molecules (molecular weight about 600 or less), of similar or diverse nature which are used for high-throughput screening analysis of the gene function, protein interaction, cellular processing, biochemical pathways, or other chemical interactions.

One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.

The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.

Cytidine 5'-(trihydrogen diphosphate). A cytosine nucleotide containing two phosphate groups esterified to the sugar moiety. Synonyms: CRPP; cytidine pyrophosphate.

A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.

A specific subtype of muscarinic receptor found in the CORPUS STRIATUM and the LUNG. It has similar receptor binding specificities to MUSCARINIC RECEPTOR M1 and MUSCARINIC RECEPTOR M2.

An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.

The process of finding chemicals for potential therapeutic use.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.

Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate.

An ester of glucose with phosphoric acid, made in the course of glucose metabolism by mammalian and other cells. It is a normal constituent of resting muscle and probably is in constant equilibrium with fructose-6-phosphate. (Stedman, 26th ed)

Cell surface proteins that bind glutamate and act through G-proteins to influence second messenger systems. Several types of metabotropic glutamate receptors have been cloned. They differ in pharmacology, distribution, and mechanisms of action.

Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids.

Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.

A group of pyrido-indole compounds. Included are any points of fusion of pyridine with the five-membered ring of indole and any derivatives of these compounds. These are similar to CARBAZOLES which are benzo-indoles.

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.

A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.

The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.

2-, 3-, or 4-Pyridinecarboxylic acids. Pyridine derivatives substituted with a carboxy group at the 2-, 3-, or 4-position. The 3-carboxy derivative (NIACIN) is active as a vitamin.

Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.

The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.

Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.

The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)

The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.

A computer simulation developed to study the motion of molecules over a period of time.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.

Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety.

The process by which two molecules of the same chemical composition form a condensation product or polymer.

The relationship between the dose of an administered drug and the response of the organism to the drug.

A family of hexahydropyridines.

Proteins prepared by recombinant DNA technology.

A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.

The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.

The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.

The action of a drug that may affect the activity, metabolism, or toxicity of another drug.

Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.

The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)

Organic compounds containing the -CO-NH2 radical. Amides are derived from acids by replacement of -OH by -NH2 or from ammonia by the replacement of H by an acyl group. (From Grant & Hackh's Chemical Dictionary, 5th ed)

The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.

Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

An enzyme that catalyzes the conversion of carbamoyl phosphate and L-aspartate to yield orthophosphate and N-carbamoyl-L-aspartate. (From Enzyme Nomenclature, 1992) EC 2.1.3.2.

Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties.

A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with ANEMIA, short stature, HYPOGONADISM, impaired WOUND HEALING, and geophagia. It is known by the symbol Zn.

Established cell cultures that have the potential to propagate indefinitely.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

Enzyme-mononucleotide interactions: three different folds share common structural elements for ATP recognition. (1/1100)

Three ATP-dependent enzymes with different folds, cAMP-dependent protein kinase, D-Ala:D-Ala ligase and the alpha-subunit of the alpha2beta2 ribonucleotide reductase, have a similar organization of their ATP-binding sites. The most meaningful similarity was found over 23 structurally equivalent residues in each protein and includes three strands each from their beta-sheets, in addition to a connecting loop. The equivalent secondary structure elements in each of these enzymes donate four amino acids forming key hydrogen bonds responsible for the common orientation of the "AMP" moieties of their ATP-ligands. One lysine residue conserved throughout the three families binds the alpha-phosphate in each protein. The common fragments of structure also position some, but not all, of the equivalent residues involved in hydrophobic contacts with the adenine ring. These examples of convergent evolution reinforce the view that different proteins can fold in different ways to produce similar structures locally, and nature can take advantage of these features when structure and function demand it, as shown here for the common mode of ATP-binding by three unrelated proteins. (+info)

A 20-kDa domain is required for phosphatidic acid-induced allosteric activation of phospholipase D from Streptomyces chromofuscus. (2/1100)

Two phospholipase D (PLD) enzymes with both hydrolase and transferase activities were isolated from Streptomyces chromofuscus. There were substantial differences in the kinetic properties of the two PLD enzymes towards monomeric, micellar, and vesicle substrates. The most striking difference was that the higher molecular weight enzyme (PLD57 approximately 57 kDa) could be activated allosterically with a low mole fraction of phosphatidic acid (PA) incorporated into a PC bilayer (Geng et al., J. Biol. Chem. 273 (1998) 12195-12202). PLD42/20, a tightly associated complex of two peptides, one of 42 kDa and the other 20 kDa, had a 4-6-fold higher Vmax toward PC substrates than PLD57 and was not activated by PA. N-Terminal sequencing of both enzymes indicated that both components of PLD42/20 were cleavage products of PLD57. The larger component included the N-terminal segment of PLD57 and contained the active site. The N-terminus of the smaller peptide corresponded to the C-terminal region of PLD57; this peptide had no PLD activity by itself. Increasing the pH of PLD42/20 to 8.9, followed by chromatography of PLD42/20 on a HiTrap Q column at pH 8.5 separated the 42- and 20-kDa proteins. The 42-kDa complex had about the same specific activity with or without the 20-kDa fragment. The lack of PA activation for the 42-kDa protein and for PLD42/20 indicates that an intact C-terminal region of PLD57 is necessary for activation by PA. Furthermore, the mechanism for transmission of the allosteric signal requires an intact PLD57. (+info)

Stimulation of P-glycoprotein-mediated drug transport by prazosin and progesterone. Evidence for a third drug-binding site. (3/1100)

P-glycoprotein is a plasma membrane protein of mammalian cells that confers multidrug resistance by acting as a broad-specificity, ATP-dependent efflux transporter of diverse lipophilic neutral or cationic compounds. Previously, we identified two positively cooperative drug-binding sites of P-glycoprotein involved in transport [Shapiro, A. B. & Ling, V. (1997) Eur. J. Biochem. 250, 130-137]. The H site is selective for Hoechst 33342 and colchicine. The R site is selective for rhodamine 123 and anthracyclines. Substrate binding to one site stimulates transport by the other. In this paper, we show that prazosin and progesterone stimulate the transport of both Hoechst 33342 and rhodamine 123. Rhodamine 123 and prazosin (or progesterone) in combination stimulate Hoechst 33342 transport in an additive manner. In contrast, Hoechst 33342 and either prazosin or progesterone interfere with each other, so that the stimulatory effect of the combination on rhodamine 123 transport is less than that of each individually. Non-P-glycoprotein-specific effects of prazosin on membrane fluidity and permeability were excluded. These results indicate the existence of a third drug-binding site on P-glycoprotein with a positive allosteric effect on drug transport by the H and R sites. This allosteric site appears to be one of the sites of photoaffinity labeling of P-glycoprotein by [125I]iodoarylazidoprazosin [Safa, A. R., Agresti, M., Bryk, D. & Tamai, I. (1994) Biochemistry 33, 256-265] and is likely not to be capable of drug transport. (+info)

Flavodoxin: an allosteric inhibitor of AMP nucleosidase from Azotobacter vinelandii. (4/1100)

Flavodoxin, which participates in nitrogen fixation, was found to be a potent allosteric inhibitor of AMP nucleosidase [EC 3.2.2.4] from Azotobacter vinelandii. It inhibited the enzyme by decreasing its affinity for ATP without affecting the maximum velocity. The inhibition constant for flavodoxin was estimated to be 10 muM, which is within the range of physiological concentration in the cells. The concentration of flavodoxin able to alter the activity in vitro suggests that this phenomenon could be of significance in the regulation of flavin biosynthesis in vivo. Flavin mononucleotide (FMN), a prosthetic group of flavodoxin, was also found to act as an allosteric inhibitor. Since no inhibitory action of apo-flavodoxin was observed, it was concluded that the FMN chromophore of the flavodoxin is responsible for the inhibition of the enzyme by this protein. (+info)

Structural elements of the gamma-aminobutyric acid type A receptor conferring subtype selectivity for benzodiazepine site ligands. (5/1100)

gamma-aminobutyric acid type A (GABAA) receptors comprise a subfamily of ligand-gated ion channels whose activity can be modulated by ligands acting at the benzodiazepine binding site on the receptor. The benzodiazepine binding site was characterized using a site-directed mutagenesis strategy in which amino acids of the alpha5 subunit were substituted by their corresponding alpha1 residues. Given the high affinity and selectivity of alpha1-containing compared with alpha5-containing GABAA receptors for zolpidem, mutated alpha5 subunits were co-expressed with beta2 and gamma2 subunits, and the affinity of recombinant receptors for zolpidem was measured. One alpha5 mutant (bearing P162T, E200G, and T204S) exhibited properties similar to that of the alpha1 subunit, notably high affinity zolpidem binding and potentiation by zolpidem of GABA-induced chloride current. Two of these mutations, alpha5P162T and alpha5E200G, might alter binding pocket conformation, whereas alpha5T204S probably permits formation of a hydrogen bond with a proton acceptor in zolpidem. These three amino acid substitutions also influenced receptor affinity for CL218872. Our data thus suggest that corresponding amino acids of the alpha1 subunit, particularly alpha1-Ser204, are the crucial residues influencing ligand selectivity at the binding pocket of alpha1-containing receptors, and a model of this binding pocket is presented. (+info)

Metal complexes as allosteric effectors of human hemoglobin: an NMR study of the interaction of the gadolinium(III) bis(m-boroxyphenylamide)diethylenetriaminepentaacetic acid complex with human oxygenated and deoxygenated hemoglobin. (6/1100)

The boronic functionalities on the outer surface of the Gd(III) bis(m-boroxyphenylamide)DTPA complex (Gd(III)L) enable it to bind to fructosamine residues of oxygenated glycated human adult hemoglobin. The formation of the macromolecular adduct can be assessed by NMR spectroscopy via observation of the enhancement of the solvent water proton relaxation rate. Unexpectedly, a strong binding interaction was also observed for the oxygenated unglycated human adult hemoglobin, eventually displaying a much higher relaxation enhancement. From relaxation rate measurements it was found that two Gd(III)L complexes interact with one hemoglobin tetramer (KD = 1.0 x 10(-5) M and 4.6 x 10(-4) M, respectively), whereas no interaction has been observed with monomeric hemoproteins. A markedly higher affinity of the Gd(III)L complex has been observed for oxygenated and aquo-met human adult hemoglobin derivatives with respect to the corresponding deoxy derivative. Upon binding, a net change in the quaternary structure of hemoglobin has been assessed by monitoring the changes in the high-resolution 1H-NMR spectrum of the protein as well as in the Soret absorption band. On the basis of these observations and the 11B NMR results obtained with the diamagnetic La(III)L complex, we suggest that the interaction between the lanthanide complex and deoxygenated, oxygenated, and aquo-met derivatives of human adult hemoglobin takes place at the 2, 3-diphosphoglycerate (DPG) binding site, through the formation of N-->B coordinative bonds at His143beta and His2beta residues of different beta-chains. The stronger binding to the oxygenated form is then responsible for a shift of the allosteric equilibrium toward the high-affinity R-state. Accordingly, Gd(III)L affinity for oxygenated human fetal hemoglobin (lacking His143beta) is significantly lower than that observed for the unglycated human adult tetramer. (+info)

Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme. (7/1100)

Sialuria is a rare inborn error of metabolism characterized by cytoplasmic accumulation and increased urinary excretion of free N-acetylneuraminic acid (NeuAc, sialic acid). Overproduction of NeuAc is believed to result from loss of feedback inhibition of uridinediphosphate-N-acetylglucosamine 2-epimerase (UDP-GlcNAc 2-epimerase) by cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac). We report the cloning and characterization of human UDP-GlcNAc 2-epimerase cDNA, with mutation analysis of three patients with sialuria. Their heterozygote mutations, R266W, R266Q, and R263L, indicate that the allosteric site of the epimerase resides in the region of codons 263-266. The heterozygous nature of the mutant allele in all three patients reveals a dominant mechanism of inheritance for sialuria. (+info)

Steric effects on multivalent ligand-receptor binding: exclusion of ligand sites by bound cell surface receptors. (8/1100)

Steric effects can influence the binding of a cell surface receptor to a multivalent ligand. To account for steric effects arising from the size of a receptor and from the spacing of binding sites on a ligand, we extend a standard mathematical model for ligand-receptor interactions by introducing a steric hindrance factor. This factor gives the fraction of unbound ligand sites that are accessible to receptors, and thus available for binding, as a function of ligand site occupancy. We derive expressions for the steric hindrance factor for various cases in which the receptor covers a compact region on the ligand surface and the ligand expresses sites that are distributed regularly or randomly in one or two dimensions. These expressions are relevant for ligands such as linear polymers, proteins, and viruses. We also present numerical algorithms that can be used to calculate steric hindrance factors for other cases. These theoretical results allow us to quantify the effects of steric hindrance on ligand-receptor kinetics and equilibria. (+info)

The site to which the effector binds is termed the allosteric site. Allosteric sites allow effectors to bind to the protein, ... The binding sites for heterotropic effectors, called allosteric sites, are usually separate from the active site yet ... This is in reference to the fact that the regulatory site of an allosteric protein is physically distinct from its active site ... In biochemistry, allosteric regulation (or allosteric control) is the regulation of a protein by binding an effector molecule ...

https://en.wikipedia.org/wiki/Allosteric_enzyme

The site to which the effector binds is termed the allosteric site or regulatory site. Allosteric sites allow effectors to bind ... Allosteric modulation occurs when an effector binds to an allosteric site (also known as a regulatory site) of an enzyme and ... Allosteric modulation of a receptor results from the binding of allosteric modulators at a different site (a "regulatory site ... the allosteric effector or ligand) to a site that is different from the active site The sequential model of allosteric ...

https://en.wikipedia.org/wiki/Allosteric_regulation

... but also to the allosteric site. From known SSRIs also paroxetine has action to the allosteric site, about half potency of ... probably through an allosteric interaction between two distinct, non-overlapping binding sites for the two different isomers on ... Allosteric serotonin reuptake inhibitor is a type of selective serotonin reuptake inhibitor (SSRI). Currently only escitalopram ... Escitalopram, thus, binds not only to the primary site, ... "Allosteric modulation of the effect of escitalopram, paroxetine ...

https://en.wikipedia.org/wiki/Allosteric_serotonin_reuptake_inhibitor

AMPAR PAMs bind to one or more allosteric sites on the AMPAR complex and potentiate the receptor. Unlike orthosteric (active/ ... This is because the AMPAR is composed of different combinations of various subunits, and the allosteric sites differ depending ... AMPA receptor positive allosteric modulators are positive allosteric modulators (PAMs) of the AMPA receptor (AMPR), a type of ... including allosteric site specificity, potency, impact (i.e., low versus high), and selectivity for AMPAR populations composed ...

https://en.wikipedia.org/wiki/AMPA_receptor_positive_allosteric_modulator

There are no known allosteric regulatory sites. Cholesterol-24 hydroxylase catalyzes the following reaction: cholesterol + ... The active site is accessed via a single entrance created by two helices (B' and F) and the β1-sheet. ... A single cholesterol molecule takes up the entirety of the active site, with the aliphatic tail of the cholesterol held in ... Binding of cholesterol results in an enzymatic conformational change and a subsequent induced fit of the active site around the ...

https://en.wikipedia.org/wiki/Cholesterol_24-hydroxylase

Evidence for an allosteric citrate-binding site". The Journal of Biological Chemistry. 257 (22): 13233-9. doi:10.1016/S0021- ... Evidence for an allosteric citrate-binding site". The Journal of Biological Chemistry. 257 (22): 13233-9. doi:10.1016/S0021- ... All three effectors (malate, oxaloacetate and citrate) bind to the same putative allosteric site. Recent studies of ... The active sites in these dimeric proteins are well separated from each other. Because malate dehydrogenase is closely tied to ...

https://en.wikipedia.org/wiki/Malate_dehydrogenase_2

"Characterization of the CHK1 allosteric inhibitor binding site." Biochemistry 48.41 (2009): 9823-9830". Biochemistry. 48 (41): ... Official website (Articles with short description, Short description is different from Wikidata, Orphaned articles from ...

https://en.wikipedia.org/wiki/CPC_Scientific

However, in contrast to competitive and uncompetitive inhibitors, mixed inhibitors bind to the allosteric site. Allosteric ... Conversely, allosteric binding that decreases the protein's affinity for substrate is negative modulation. At the active site, ... The binding of a ligand to an allosteric site of a multimeric enzyme often induces positive cooperativity, that is the binding ... Citrate, an intermediate of the citric acid cycle, also works as an allosteric regulator of PFK. Binding sites can be ...

https://en.wikipedia.org/wiki/Binding_site

The CB1 receptor possesses an allosteric modulatory binding site. The CB1 receptor is a pre-synaptic heteroreceptor that ... Nguyen T, Li JX, Thomas BF, Wiley JL, Kenakin TP, Zhang Y (May 2017). "Allosteric Modulation: An Alternate Approach Targeting ... November 2005). "Allosteric modulation of the cannabinoid CB1 receptor". Molecular Pharmacology. 68 (5): 1484-1495. doi:10.1124 ... Effects may vary based on the site of cannabinoid application, input from higher cortical centers, and whether drug application ...

https://en.wikipedia.org/wiki/Cannabinoid_receptor_type_1

... which bind to and block the glycine site; noncompetitive antagonists, which inhibit NMDARs by binding to allosteric sites; and ... Lipina T, Labrie V, Weiner I, Roder J (April 2005). "Modulators of the glycine site on NMDA receptors, D-serine and ALX 5407, ... Banks P, Franks NP, Dickinson R (March 2010). "Competitive inhibition at the glycine site of the N-methyl-D-aspartate receptor ... Aptiganel (Cerestat, CNS-1102): binds the Mg2+ binding site within the channel of the NMDA receptor. HU-211: an enantiomer of ...

https://en.wikipedia.org/wiki/NMDA_receptor_antagonist

... active site inhibitors, allosteric site inhibitors and miscellaneous site inhibitors. The miscellaneous site inhibitors are ... NS5B also has allosteric sites in addition to the active site. Palm I, domain close to the active site, palm II, partly ... at allosteric binding sites, the enzyme active site, or the pyrophosphate binding site, respectively. Nucleoside analogue ... active site inhibitors, allosteric site inhibitors, and miscellaneous non-nucleoside inhibitors. For miscellaneous non- ...

https://en.wikipedia.org/wiki/NS5B_inhibitor

Inhibitors of this allosteric site are classified as type III inhibitors. Another possible target is the T-loop of CDK2. When ... Recently, the availability of new CDK crystal structures led to the identification of a potential allosteric binding site near ... binds at the active site located between the N and C lobes of the kinase. Due to the location of the active site, partner ... The significance of this movement is that it brings the side chain of Glu 51, which belongs to a triad of catalytic site ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_2

"Characterization of the allosteric anion-binding site of O-acetylserine sulfhydrylase". Biochemistry. 40 (25): 7446-52. doi: ...

https://en.wikipedia.org/wiki/Cysteine_synthase

Usenik A, Legiša M (23 November 2010). "Evolution of allosteric citrate binding sites on 6-phosphofructo-1-kinase". PLOS ONE. 5 ... In particular, the binding site for the PFK inhibitor citrate is found in the PFKL C-terminal region. This gene encodes one of ... N-terminal of the subunits carries out their catalytic activity while the C-terminal contains allosteric ligand binding sites. ... Abnormal splicing of the muscle phosphofructokinase gene due to a point mutation at the 5'-splice site". The Journal of ...

https://en.wikipedia.org/wiki/PFKM

... non-competitive antagonists can either bind to the ligand site or other site called the allosteric site. A receptor's agonist ... If the non-competitive antagonist binds to the allosteric site and an agonist binds to the ligand site, the receptor will ... A competitive antagonist will attach itself to the same binding site of the receptor that the agonist will bind to. Even though ... does not bind to its allosteric binding site. The binding of a non-competitive antagonist is irreversible. ...

https://en.wikipedia.org/wiki/Adrenergic_antagonist

When ATP binds to the allosteric activity site, it activates RNR. In contrast, when dATP binds to this site, it deactivates RNR ... RNR1 contains both allosteric sites, mediating regulation of substrate specificity and activity. Depending on the allosteric ... In all classes, binding of ATP or dATP to the allosteric site induces reduction of cytidine 5'-diphosphate (CDP) and uridine 5 ... in the active site. Site-directed mutations of the RNR primary structure indicate that all residues cited above participate in ...

https://en.wikipedia.org/wiki/Ribonucleotide_reductase

Antagonists mediate their effects by binding to the active site or to the allosteric site on a receptor, or they may interact ... This may be accomplished by binding to the active site or the allosteric site. In addition, antagonists may interact at unique ... by binding to an allosteric site of the receptor, or by irreversibly binding to the active site of the receptor. The former ... act at an allosteric site. These antagonists bind to a distinctly separate binding site from the agonist, exerting their action ...

https://en.wikipedia.org/wiki/Receptor_antagonist

Allosteric activators such as AMP and ADP bind to the allosteric site as to facilitate the formation of the R state by inducing ... On the opposite side of the each subunit from each active site is the allosteric site, at the interface between subunits in the ... binding site as well as a separate allosteric binding site. Each subunit of the tetramer is 319 amino acids and consists of two ... Similarly, inhibitors such as ATP and PEP bind to the same allosteric site and facilitate the formation of the T state, thereby ...

https://en.wikipedia.org/wiki/Phosphofructokinase_1

In mixed inhibition, the inhibitor binds to an allosteric site, i.e. a site different from the active site where the substrate ... However, not all inhibitors that bind at allosteric sites are mixed inhibitors. Mixed inhibition may result in either: A ...

https://en.wikipedia.org/wiki/Mixed_inhibition

Without access to the allosteric site, the NNRTI will not be effective. Integrase inhibitors prevent the HIV integrase enzyme ... Non-nucleoside reverse transcriptase inhibitors (NNRTI) inhibit reverse transcriptase by binding to an allosteric site on it. ... Protease inhibitors bind to the active site of the viral protease, which prevents the cleavage of the Gag and Gagpol proteins. ...

https://en.wikipedia.org/wiki/Resistance_mutation_(virology)

"Crystal structure of human phosphoribosylpyrophosphate synthetase 1 reveals a novel allosteric site". Biochemical Journal. 401 ...

https://en.wikipedia.org/wiki/Phosphoribosyl_pyrophosphate

"Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site". Nature Structural Biology. 9 (4): 268-72. doi: ... ISBN 978-3-527-68303-1. Noren CJ, Anthony-Cahill SJ, Griffith MC, Schultz PG (1989). "A general method for site-specific ... Carolyn Bertozzi's research group has developed methods for site-specifically reacting molecules at the surface of cells via ... In addition, researchers have used unnatural amino acid mutagenesis at targeted sites within a peptide sequence. Advances in ...

https://en.wikipedia.org/wiki/Chemical_biology

"Crystal structure of human phosphoribosylpyrophosphate synthetase 1 reveals a novel allosteric site". Biochemical Journal. 401 ...

https://en.wikipedia.org/wiki/5-Aminoimidazole_ribotide

ATP competes with AMP for the allosteric effector site on the PFK enzyme. ATP concentrations in cells are much higher than ... Thus, the relevance of ATP as an allosteric effector is questionable. An increase in AMP is a consequence of a decrease in ... Allosteric inhibition and activation by metabolites: In particular end-product inhibition of rate limiting enzymes by ... Allosteric inhibition and activation by Protein-protein interactions (PPI). Indeed, some proteins interact with and regulate ...

https://en.wikipedia.org/wiki/Glycolysis

Its main responsibility is to maintain allosteric control of the kinase active site. This control manifests in CDK-cyclin ... It is important to note that in CDK 1, 2 and 6, the T-loop and a separate C-terminal region are the major sites of cyclin ... These cyclin binding sites are the regions of highest variability in CDKs despite relatively high sequence homology surrounding ... After the hydrolysis of ATP to phosphorylate at this site, these complexes are able to complete their intended function, the ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_complex

Christopoulos, A. (2002) Allosteric binding sites on cell-surface receptors: Novel targets for drug discovery. Nature Rev. Drug ... Multi-site Pharmacology: Recommendations for the nomenclature of receptor allosterism and allosteric ligands. Pharmacol. Rev. ... Allosteric modulation of endogenous metabolites as an avenue for drug discovery. Mol Pharmacol., 2012, 82(2):281-90. Valant, C ... Arthur Christopoulos' research focuses on allosteric mechanisms of drug action and signal-pathway biased agonism at G protein- ...

https://en.wikipedia.org/wiki/Arthur_Christopoulos

October 2018). "Intracellular Binding Site for a Positive Allosteric Modulator of the Dopamine D1 Receptor". Molecular ... January 2017). "An Allosteric Potentiator of the Dopamine D1 Receptor Increases Locomotor Activity in Human D1 Knock-In Mice ... In 2015 the first positive allosteric modulator for the human D1 receptor was discovered by high-throughput screening. Several ... May 2021). "Mechanism of dopamine binding and allosteric modulation of the human D1 dopamine receptor". Cell Research. 31 (5): ...

https://en.wikipedia.org/wiki/Dopamine_receptor_D1

However, there may be unoccupied allosteric binding sites that may be of interest. Furthermore, it may be that only apoprotein ... Binding site identification is the first step in structure based design. If the structure of the target or a sufficiently ... In brief, binding site identification usually relies on identification of concave surfaces on the protein that can accommodate ... Yuan Y, Pei J, Lai L (Dec 2013). "Binding site detection and druggability prediction of protein targets for structure-based ...

https://en.wikipedia.org/wiki/Drug_design

A common drug, diazepam, acts as an allosteric enhancer at this binding site. Another receptor for GABA, known as GABAB, can be ... The most common of these binding sites, benzodiazepine, allows for both agonist and antagonist effects on the receptor. ... Sigel, E (2002). "Mapping of the benzodiazepine recognition site on GABA(A) receptors". Current Topics in Medicinal Chemistry. ... a molecule that binds to a receptor protein on a different site than that of the agonist, but causes a conformational change in ...

https://en.wikipedia.org/wiki/Neuropharmacology

Under resting conditions, it is thought that chloride is bound to allosteric sites in prestin. Upon deflection of the basilar ... Intracellular chloride dissociates from the allosteric binding sites in prestin, causing contraction of prestin. Upon BM ... Additionally, Ca2+ briefly binds to a cytostolic site on the MET channel which is estimated to be only 5 nm from the channel ... Due to the differences in calcium concentration at the cytostolic binding site when calcium is bound to the MET channel versus ...

https://en.wikipedia.org/wiki/Cochlear_amplifier

OPRTase, as a member of type I PRTases, has a prominent loop next to its active site. It is flexible in its open state and can ... OMP is an allosteric activator of OMP decarboxylase activity. At low enzyme concentration and low OMP concentrations, OMP ... These two sites catalyze the last two steps of the de novo uridine monophosphate (UMP) biosynthetic pathway. After addition of ... For catalysis to occur, a dimer must exist in which a loop from one subunit covers the active site from the other one. In ...

https://en.wikipedia.org/wiki/Uridine_monophosphate_synthase

... and an allosteric monomer (E-allo). Heme binds only to the peroxidase site of E-cat while substrates, as well as certain ... Each monomer of the enzyme has a peroxidase and a PTGS (COX) active site. The PTGS (COX) enzymes catalyze the conversion of ... Second, PGG2 is reduced to PGH2 in the peroxidase active site. The synthesized PGH2 is converted to prostaglandins (PGD2, PGE2 ... Both the cyclooxygenase and the peroxidase active sites are located in the catalytic domain, which accounts for approximately ...

https://en.wikipedia.org/wiki/Prostaglandin-endoperoxide_synthase_2

Giorgi O, Corda MG, Gritti I, Mariotti M, Ongini E, Biggio G (July 1989). "Binding sites for [3H]2-oxo-quazepam in the brain of ... GABAA receptor positive allosteric modulators, Thioamides, Trifluoromethyl compounds). ... Quazepam modulates specific GABAA receptors via the benzodiazepine site on the GABAA receptor. This modulation enhances the ... "Preferential affinity of 3H-2-oxo-quazepam for type I benzodiazepine recognition sites in the human brain". Life Sci. 42 (2): ...

https://en.wikipedia.org/wiki/Quazepam

When lormetazepam binds to the benzodiazepine receptor sites in sufficient quantities it produces sedation which is used ... GABAA receptor positive allosteric modulators, Lactams, Lactims). ...

https://en.wikipedia.org/wiki/Lormetazepam

The active site of OST is located about 4 nm from the lumenal face of the ER membrane. It usually acts during translation as ... Karaoglu D, Kelleher DJ, Gilmore R (October 2001). "Allosteric regulation provides a molecular mechanism for preferential ... Nilsson IM, von Heijne G (March 1993). "Determination of the distance between the oligosaccharyltransferase active site and the ...

https://en.wikipedia.org/wiki/Oligosaccharyltransferase

... binds at a distinct binding site associated with a Cl− ionophore at the GABAA receptor, increasing the duration of ... GABAA receptor positive allosteric modulators, Allyl compounds, All stub articles, Sedative stubs). ...

https://en.wikipedia.org/wiki/Talbutal

... exhibit increased reactivity when the catalyst molecule is modified at a site distinct from the catalyst site. Gianneschi ... Gianneschi, Nathan C.; Cho, So-Hye; Nguyen, SonBinh T.; Mirkin, Chad A. (2004). "Reversibly Addressing an Allosteric Catalyst ... "PI: Nathan C. Gianneschi , The Gianneschi Group". sites.northwestern.edu. Retrieved 2021-05-29. "Nathan C. Gianneschi named ... There, he developed supramolecular catalysts that exhibit allosteric behavior, that is, ...

https://en.wikipedia.org/wiki/Nathan_C._Gianneschi

Glucose 6-phosphate binds to an allosteric site, resulting in conformational changes to SPS that increase the enzyme's affinity ... Inorganic phosphate can also bind to this allosteric site, preventing glucose 6-phosphate activation of SPS. Like regulation ... SPS-kinase reversibly phosphorylates a serine residue and subsequently deactivates SPS, In spinach and maize, the site of ... and is an excellent example of various key enzyme regulation strategies such as allosteric control and reversible ...

https://en.wikipedia.org/wiki/Sucrose-phosphate_synthase

Wang Y, Guo L, Jiang HF, Zheng LT, Zhang A, Zhen XC (May 2016). "Allosteric Modulation of Sigma-1 Receptors Elicits Rapid ... January 2009). "Substituted benzo[d]oxazol-2(3H)-one derivatives with preference for the sigma1 binding site". European Journal ... Vavers E, Zvejniece L, Veinberg G, Svalbe B, Domracheva I, Vilskersts R, Dambrova M (2015). "Novel positive allosteric ... June 2015). "A SIGMAR1 splice-site mutation causes distal hereditary motor neuropathy". Neurology. 84 (24): 2430-2437. doi: ...

https://en.wikipedia.org/wiki/Sigma-1_receptor

Myo-inositol trispyrophosphate (ITPP), also known as compound number OXY111A, is an allosteric effector of hemoglobin which ... it has also been hypothesized that replacement of Fe2+ by Co2+ in the hydroxylase active site could be a contributing factor to ...

https://en.wikipedia.org/wiki/Blood_doping

First, arrestin binding to the cytoplasmic face of the receptor occludes the binding site for heterotrimeric G-protein, ... Smith JS, Lefkowitz RJ, Rajagopal S (January 2018). "Biased signalling: from simple switches to allosteric microprocessors". ... Increased accessibility of these sites in receptor-bound arrestin targets the arrestin-receptor complex to the coated pit. ... the movement of the two arrestin domains and the release of its C-terminal tail that contains clathrin and AP2 binding sites. ...

https://en.wikipedia.org/wiki/Arrestin

It reverses the effects of benzodiazepines by competitive inhibition at the benzodiazepine (BZ) recognition site on the GABA/ ... Benzodiazepine overdose Benzodiazepine Bretazenil Imidazenil Ro15-4513 GABAA receptor negative allosteric modulators Hunkeler, ... Danka Pericic; Josipa Lazic & Dubravka Svob Strac (August 2005). "Chronic treatment with flumazenil enhances binding sites for ... Flumazenil competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor ...

https://en.wikipedia.org/wiki/Flumazenil

The company proceeded to show that MLR-1023 is an allosteric activator of Lyn kinase with an EC50 of 63 nM. As of 2012 Melior ... "Melior Discovery website press releases". "Melior Pharmaceuticals Announces Positive Phase 2A Results in Type 2 Diabetes Study ... Saporito MS, Ochman AR, Lipinski CA, Handler JA, Reaume AG (2011). "MLR-1023 is potent and selective allosteric activator of ...

https://en.wikipedia.org/wiki/Tolimidone

Alternatively, the inhibitor can bind to a site remote from the enzyme active site. These are known as allosteric ("alternative ... This results from the active site containing two different binding sites within the active site, one for each substrate. For ... In some cases, the inhibitor may bind to a distinct site on the enzyme that is in allosteric communication with the substrate ... The binding site of inhibitors on enzymes is most commonly the same site that binds the substrate of the enzyme. These active ...

https://en.wikipedia.org/wiki/Enzyme_inhibitor

... they affect the receptor by binding at a different site on the protein. This is called allosteric modulation. In ... In pharmacology, GABAA receptor positive allosteric modulators are positive allosteric modulator (PAM) molecules that increase ... For example, the binding site of neurosteroids in the GABAA receptor is not known and barbiturates bind at a beta subunit that ... An α2, α3 and/or α5 selective positive allosteric agonist, like L-838,417 for example, might be useful as an analgesic drug ...

https://en.wikipedia.org/wiki/GABAA_receptor_positive_allosteric_modulator

The unstructured region at the very end of the C-terminal is believed to be the docking site for co-chaperones. The heat shock ... The two terminal domains are linked together by a conserved region referred to as loop LL,1, which is critical for allosteric ... oncofetal proteins and products and transporting them into intracellular sites, thereby promoting tumor cell proliferation. As ...

https://en.wikipedia.org/wiki/HSPA8

... the active site, and the FAD and NAD(+)-binding sites. The DLD homodimer functions as the E3 component of the pyruvate, α- ... This protein may use the morpheein model of allosteric regulation. Lipoic acid GRCh38: Ensembl release 89: ENSG00000091140 - ... structure is different in that it has two loops that extend from the general protein structure and into the FAD binding sites ...

https://en.wikipedia.org/wiki/Dihydrolipoamide_dehydrogenase

... allosteric site - allostery - allotrope - allotropy - alpha adrenergic receptor - alpha helix - alpha-1 adrenergic receptor - ... active site - active transport - adenosine - adenosine diphosphate (ADP) - adenosine monophosphate (AMP) - adenosine ...

https://en.wikipedia.org/wiki/Index_of_biochemistry_articles

... but same-site binding is not a requirement. A competitive inhibitor could bind to an allosteric site of the free enzyme and ... as long as it does not bind to the allosteric site when the substrate is bound. For example, strychnine acts as an allosteric ... The active site is a region on an enzyme to which a particular protein or substrate can bind. The active site will thus only ... This is accomplished by blocking the binding site of the substrate - the active site - by some means. The Vmax indicates the ...

https://en.wikipedia.org/wiki/Competitive_inhibition

HER2 is an allosteric activator of E6AP, and lies at the most commonly deleted region in AS. Its deletion could result in the ... At the site of doubles stranded breaks, HERC2 facilitates the binding of RNF8, a RING finger ubiquitin ligase to the E2 ... XPA is involved in recognising DNA damage and provides a scaffold for other repair factors to bind at the damage site. HERC2 ... Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific ...

https://en.wikipedia.org/wiki/HERC2

It acts as a positive allosteric modulator of the benzodiazepine site of the GABAA receptor. Wogonin at chemblink.com Hui KM, ... GABAA receptor positive allosteric modulators, All stub articles, Anticonvulsant stubs). ...

https://en.wikipedia.org/wiki/Wogonin

... an allosteric site on the MAO enzyme). Clorgyline Rasagiline Selegiline Fisar Z, Hroudová J, Raboch J (2010). "Inhibition of ...

https://en.wikipedia.org/wiki/Pargyline

Official website Washington Post July 20, 2019 "An onslaught of pills, hundreds of thousands of deaths: Who is accountable?" " ... it would acquire VM Pharma in the process gaining access to worldwide development and commercial rights to an allosteric ... the company's website said it had some 1,700 people on its payroll. That same month, the company announced ... Its manufacturing takes place at three sites: Purdue Pharmaceuticals L.P., a plant located in Wilson, North Carolina, the P.F. ...

https://en.wikipedia.org/wiki/Purdue_Pharma

"Arginine 54 in the active site of Escherichia coli aspartate transcarbamoylase is critical for catalysis: A site-specific ... Stevens, R. C., & Lipscomb, W. N., "Allosteric Enzymes" Eds., R. Diamond, T. F. Koetzle, K. Prout, & J. Richardson, Molecular ... in the chemistry department at Harvard University where he focused on the large allosteric enzyme aspartate ... Two disparate ligand binding sites in the human P2Y1 receptor Nature 520: 317-321 Y. Kang, X. E. Zhou, X. Gao, Y. He, W. Liu, A ...

https://en.wikipedia.org/wiki/Raymond_C._Stevens

The sliding-rebinding model differs from the allosteric model in that the allosteric model posits that only one binding site ... With multiple binding sites, and even the ability to re-associate with the original binding site, the rate of ligand ... The allosteric model claims that tension on the EGF domain favors the extended conformation, and extension of this domain ... The main domains involved in these states are a lectin domain which contains the ligand binding site and an EGF domain which ...

https://en.wikipedia.org/wiki/Catch_bond

Also, the binding of the Kinesin-5 inhibitors to an allosteric site on the motor interrupts the mechanism by which this enzyme ... These structural changes are correlated with other changes in the catalytic active site. Other sites of inhibitor binding have ... This toolkit of allosteric inhibitors has been used to probe the specific role of Kinesin-5 in mitotic spindle assembly as well ... Kim ED, Buckley R, Learman S, Richard J, Parke C, Worthylake DK, Wojcik EJ, Walker RA, Kim S (2010). "Allosteric drug ...

https://en.wikipedia.org/wiki/Kinesin-like_protein_KIF11

Pruzan R, Pongracz K, Gietzen K, Wallweber G, Gryaznov S (January 2002). "Allosteric inhibitors of telomerase: oligonucleotide ... hTR is directly transcribed from a dedicated promoter site located at genomic locus 3q26.2 by RNA polymerase II. Mature hTR is ...

https://en.wikipedia.org/wiki/Telomerase_RNA_component

... glycogen binding sites, allosteric sites, and a reversibly phosphorylated serine residue. First, the catalytic sites are ... This site was not sensitive to the same inhibitors as those at the AMP allosteric site, and most success has been had ... Å from the catalytic site . This site is most likely the site at which the enzyme binds to glycogen granules before initiating ... The allosteric site of AMP binding on muscle isoforms of glycogen phosphorylase are close to the subunit interface just like ...

https://en.wikipedia.org/wiki/Glycogen_phosphorylase

Feng C, Post CB (February 2016). "Insights into the allosteric regulation of Syk association with receptor ITAM, a multi-state ... SFKs have multiple phosphorylation sites that regulate their catalytic activity. If the kinase is associated with an NTR, ... Phosphorylated tyrosine residues in cytoplasmic tails of NTRs serve as docking sites for SH2 domains of cytosolic signalling ...

https://en.wikipedia.org/wiki/Non-catalytic_tyrosine-phosphorylated_receptor

The novelty and the advantages of the screening platform, the allosteric binding site addressed by these new ligands and the ... Pharmacological folding chaperones act as allosteric ligands of Frizzled4 Nat Chem Biol. 2015 Apr;11(4):280-6. doi: 10.1038/ ...

https://pubmed.ncbi.nlm.nih.gov/25751279/?dopt=Abstract

The list of proteins under allosteric regulation includes AGC protein kinases. AGC kinases have a conserved allosteric site, ... Bidirectional Allosteric Communication between the ATP-Binding Site and the Regulatory PIF Pocket in PDK1 Protein Kinase. ... Analytics cookies help website owners to understand how visitors interact with websites by collecting and reporting information ... Preference cookies enable a website to remember information that changes the way the website behaves or looks, like your ...

https://research.pasteur.fr/en/publication/bidirectional-allosteric-communication-between-the-atp-binding-site-and-the-regulatory-pif-pocket-in-pdk1-protein-kinase/

translation of ALLOSTERIC SITE,translations from English,translation of ALLOSTERIC SITE English ... translations of ALLOSTERIC SITE. translation of ALLOSTERIC SITE in French - see translations ...

http://translation.sensagent.com/translate/allosteric+site/en/multilingual.html

Changes related to "Allosteric site". From The School of Biomedical Sciences Wiki ...

https://teaching.ncl.ac.uk/bms/wiki/index.php?title=Special:RecentChangesLinked&limit=500&hideliu=1&hidemyself=1&target=Allosteric_site

The PIF-pocket of AGC protein kinases participates in the physiologic mechanism of regulation by acting as a docking site for ... Substrate-Selective Inhibition of Protein Kinase PDK1 by Small Compounds that Bind to the PIF-Pocket Allosteric Docking Site ... Substrate-Selective Inhibition of Protein Kinase PDK1 by Small Compounds that Bind to the PIF-Pocket Allosteric Docking Site. ... The PIF-pocket of AGC protein kinases participates in the physiologic mechanism of regulation by acting as a docking site for ...

https://hal-pasteur.archives-ouvertes.fr/pasteur-03137915

EPFL scientists have created a new computer model that can help better design of allosteric drugs, which control proteins at a ... The main reason allosteric sites are of such interest to drug design is that they can be used to inhibit or improve the ... For example, diazepam (Valium) acts on an allosteric site of the GABAA receptor in the brain, and increases its binding ability ... Developing an allosteric model. Despite the importance of allosteric processes, we still do not fully understand how a molecule ...

https://www.news-medical.net/news/20170221/EPFL-scientists-develop-new-computer-model-for-betterc2a0design-of-allosteric-drugs.aspx

Dissecting Structure-Encoded Determinants of Allosteric Cross-Talk between Post-Translational Modification Sites in the Hsp90 ... To study how the large electrostatic perturbations in c-Src3MΔC might shift pKa values of active site residues, we performed ... Essential ion pair dynamics in the active site of c-Src. To probe the effects of ATP-binding and Y416 phosphorylation on Src ... Characterization of sites for tyrosine phosphorylation in the transforming protein of Rous sarcoma virus (pp60v-src) and its ...

https://www.nature.com/articles/srep43996?error=cookies_not_supported&code=e3b09be0-e8ee-40ca-9fb9-b54f082866a1

An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. In: Science Signaling. 2020 ; Vol. 18, No. 646. ... An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. Science Signaling. 2020 Aug;18(646):aba3043. doi: ... An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. / Gannam, Zachary T.K.; Min, Kisuk; Shillingford, ... Dive into the research topics of An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. Together they ...

https://scholars.mssm.edu/en/publications/an-allosteric-site-on-mkp5-reveals-a-strategy-for-small-molecule--2

Allosteric binding sites, elsewhere on the receptors, are less well-defined, and so less exploited clinically. We report the ... Diversity in location, mechanism, and selectivity of allosteric ligands provides potential to expand the range of receptor ... a positive allosteric modulator of this receptor. It binds on the receptors inner surface in a pocket created by intracellular ... primary binding site of G protein-coupled receptors are the most common therapeutics. ...

https://ui.adsabs.harvard.edu/abs/2019Sci...364.1283L

Evolutionary plasticity in the allosteric regulator-binding site of pyruvate kinase isoform PykA from Pseudomonas aeruginosa. ... for this site.. Copyright © 2022 Elsevier Inc. except certain content provided by third parties. The content on this site is ... Enzyme kinetics assays revealed that PykA displays potent K-type allosteric activation by glucose 6-phosphate and by ...

https://www.jbc.org/Microbiology?startPage=&KeywordRaw=bacterial%20metabolism

Candidate Binding Sites for Allosteric Inhibition of the SARS-CoV-2 Main Protease from the Analysis of Large-Scale Molecular ... Candidate Binding Sites for Allosteric Inhibition of the SARS-CoV-2 Main Protease from the Analysis of Large-Scale Molecular ... Based on this analysis we propose some relevant contact patterns and three possible binding sites which could be targeted to ... Based on this analysis we propose some relevant contact patterns and three possible binding sites which could be targeted to ...

https://iris.sissa.it/handle/20.500.11767/125971

... to discover allosteric sites. It reproduced the known allosteric site for MDL-801 on Sirt6 and uncovered a novel cryptic ... Discovery of cryptic allosteric sites using reversed allosteric communication by a combined computational and experimental ... Please enable JavaScript to access the full features of the site or access our non-JavaScript page. ... A structural ensemble derived from cryo-electron microscopy reveals a cryptic pocket site in intermediate states along the ...

https://pubs.rsc.org/en/journals/articlecollectionlanding?sercode=sc&themeid=af6970b2-9e7b-4092-b00c-b162aeb9f645

Inhibition of RAS function through targeting an allosteric regulatory site. Smith M, Koide A, Zhou Y, Eguchi RR, Sha F, Gajwani ... MEK drives BRAF activation through allosteric control of KSR proteins. Lavoie H, Sahmi M, Maisonneuve P, Marullo SA, ...

https://www.iric.ca/en/research/principal-investigators/marc-therrien

In response to studies that suggested the presence of several binding regions within the CYP3A4 active site, multiple probe ... Homotropic Allosteric Mechanism of Site-Specific Hydroxylation.. *I. Denisov, Y. Grinkova, Tyler Camp, M. McLean, S. Sligar ... By clicking accept or continuing to use the site, you agree to the terms outlined in our. Privacy Policy (opens in a new tab), ... In response to studies that suggested the presence of several binding regions within the CYP3A4 active site, multiple probe ...

https://www.semanticscholar.org/paper/Selection-of-Alternative-CYP3A4-Probe-Substrates-In-Foti-Rock/9f709f6e61368c21b8e66deeef35934b4ed3e5e8

Each of these mutations changes a single amino acid in a region of the enzyme known as the allosteric site. This region is ... Mutations in the allosteric site disrupt this feedback mechanism, resulting in an overproduction of sialic acid. This simple ... Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the ... MedlinePlus also links to health information from non-government Web sites. See our disclaimer about external links and our ...

https://medlineplus.gov/genetics/gene/gne/

Allosteric Site. 2. 2019. 113. 0.340. Why? Epithelial-Mesenchymal Transition. 1. 2013. 713. 0.340. Why? ...

https://connects.catalyst.harvard.edu/Profiles/display/Person/154084/Network/ResearchAreas/details

Compounds that bind to allosteric sites offer many benefits over those which interact orthosterically. These include enhanced ... A number of allosteric compounds have been identified in multiple disease areas including CNS (physiological and neuropathic ... Allosteric activity was also determined for receptor internalization and provides the means to examine the effect of ... Allosteric approaches provide opportunities for new drug discovery by overcoming ligand incompatibility with certain drug ...

https://discoverx.com/tools-resources/document-resource-library/documents/2015-slas-conference-poster-interrogating-alloster

After local rearrangement, the allosteric site serves as a CK2 beta interface. This opens the potential to construct molecules ... Our website will not work properly. Please update to a newer version or download a new web browser, such as Chrome or Firefox. ... but additionally it occupies an allosteric site that can be alternatively filled by glycerol. Inhibition kinetic studies ... Evolved to be active: sulfate ions define substrate recognition sites of CK2alpha and emphasise its exceptional role within the ...

https://www.rcsb.org/structure/3H30

Enzyme regulation: from allosteric sites to intracellular behavior, A. Sols, C. Cancedo and J.J. Aragon. Jean Brachet (1909- ... a new browser tab will open so you can complete the survey after you have completed your visit to this website.. Thanks in ...

https://www.elsevier.com/books/selected-topics-in-the-history-of-biochemistry-personal-recollections-part-iii/semenza/978-0-444-81216-2

Allosteric quinoxaline-based inhibitors of the flavivirus NS2B/NS3 protease Tuesday, November 29, 2022 ... GSBS Website. UMMS Career Development. Office for Postdoctoral Scholars. UMMS Chemical Biology. UMMS Intranet. UMMS News. UMMS ...

https://www.umassmed.edu/alilab/

There are also multiple other allosteric ligand binding sites on GABAA receptors, where ligands that bind have a modulatory ... For example, ethanol binds with high affinity to δ-subunits and with low affinity to an allosteric transmembrane binding site ... 0830), also bind to multiple allosteric transmembrane binding sites, and binding increases the duration of ion channel opening ... Home / Pharmacology / Ion Channels / Ligand-gated Ion Channels / GABAA and GABAA-ρ Receptors / GABAA Receptors ...

https://www.tocris.com/pharmacology/gabaa-receptors

to inactivate (a gene or formation of a gene product) by allosteric combination at a DNA binding site ... to inactivate (a gene or formation of a gene product) by allosteric combination at a DNA binding site ... Recent Examples on the Web. Verb. Younger LGBTQ Southerners, those ages 18-24, were also more likely to report that a caregiver ...

https://www.merriam-webster.com/dictionary/repress

Shanina, E.; Kuhaudomlarp, S.; Lal, K.; Seeberger, P. H.; Imberty, A.; Rademacher, C.: Druggable allosteric sites in β- ... Intradomain allosteric network modulates calcium affinity of the C-Type lectin receptor langerin. Journal of the American ... evolution of active-site SHP2 inhibitors based on scaffold hopping and bioisosteric replacement. Journal of Medicinal Chemistry ... Identification of multiple druggable secondary sites by fragment screening against DC-SIGN. Angewandte Chemie International ...

https://www.mpikg.mpg.de/publication-search/5172719?person=%2Fpersons%2Fresource%2Fpersons217567

Riederer EA, Moënne-Loccoz P, Valiyaveetil FI. Distinct roles of the Na+ binding sites in the allosteric coupling mechanism of ... Rational Design of a Histidine-Methionine Site Modeling the M-Center of Copper Monooxygenases in a Small Metallochaperone ... Sites and sources of sympathoexcitation in obese male rats: role of brain insulin. Am J Physiol Regul Integr Comp Physiol. 2020 ... Investigation of the allosteric coupling mechanism in a glutamate transporter homolog via unnatural amino acid mutagenesis. ...

https://www.ohsu.edu/school-of-medicine/chemical-physiology-and-biochemistry/publications

... with high binding affinity to key allosteric-site residues. The binding energies revealed that glucosinalbin and glucomoringin ... We have just recently launched a new version of our website.. Help us to further improve by taking part in this short 5 minute ... High Visibility: indexed within Scopus, ESCI (Web of Science), Embase, CAPlus / SciFinder, and other databases. ... We use cookies on our website to ensure you get the best experience.. Read more about our cookies here. ...

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Eg5 - New allosteric binding site. 3zfc. Crystal Structure of the Kif4 Motor Domain Complexed With Mg-AMPPNP. ... The surrounding active site residues are almost perfectly superimposable in the two structures and the hydrogen-bonding ... These structures reveal the location of the nucleotide complexes and define the amino acid residues that form the active site. ... The pyrophosphate molecule occupies the beta- and gamma-phosphate sites, where the two phosphorus atoms are in the same ...

https://smart.embl.de/smart/do_annotation.pl?DOMAIN=Blast:KISc&START=103&END=239&E_VALUE=5e-41&TYPE=BLAST&BLAST=MADKILPQRIRELVPESQAYMDLLAFERKLDQTIMRKRVDIQEALKRPMKQKRKLRLYISNTFNPAKPDAEDSDGSIASWELRVEGKLLDDPSKQKRKFSSFFKSLVIELDKDLYGPDNHLVEWHRTPTTQETDGFQ

... including allosteric inhibitors that bind distal to the active site. We employ molecular modeling and simulation to understand ... Our studies highlight mechanisms of allosteric regulation that provide insight into how allosteric inhibitors decrease enzyme ... Allosteric regulation is a key way in which protein function can be modulated in biological systems. Thus, better comprehending ... Understanding how allosteric inhibitors modulate the function of the HCV polymerase provides insight into what intrinsic ...

https://www.biophysics.org/blog/using-biophysics-to-understand-the-basis-of-allosteric-inhibition-in-the-hepatitis-c-virus-polymerase

AMP activates AMPK by promoting its phosphorylation at Thr 172 and by direct activation via an allosteric AMP site. Since ... Metformins primary site of action is the respiratory chain Andrew P Halestrap ... The possibility that metformin could be a direct allosteric AMPK activator was excluded by showing that, when incubated with ...

https://www.jci.org/articles/view/13505?content_type=full

Discovery of an Allosteric Binding Site in Kinetoplastid Methionyl-tRNA Synthetase. Torrie, L. S., Robinson, D. A., Thomas, M. ... Defluorination Capability of l-2-Haloacid Dehalogenases in the HAD-Like Hydrolase Superfamily Correlates with Active Site ...

https://discovery.dundee.ac.uk/en/organisations/drug-discovery-unit/publications/?type=%2Fdk%2Fatira%2Fpure%2Fresearchoutput%2Fresearchoutputtypes%2Fcontributiontojournal%2Farticle&ordering=type&descending=false&page=1

The list of proteins under allosteric regulation includes AGC protein kinases. (pasteur.fr)
The PIF-pocket of AGC protein kinases participates in the physiologic mechanism of regulation by acting as a docking site for substrates and as a switch for the transduction of the conformational changes needed for activation or inhibition. (archives-ouvertes.fr)
This "at a distance" approach is called "allosteric regulation", and predicting allosteric pathways for enzymes and other proteins has gathered considerable interest. (news-medical.net)
Allosteric regulation is a fundamental molecular mechanism that modulates numerous cell processes, fine-tuning them and making them more efficient. (news-medical.net)
Enzyme regulation: from allosteric sites to intracellular behavior, A. Sols, C. Cancedo and J.J. Aragon. (elsevier.com)
We employ molecular modeling and simulation to understand the physical processes that underlie this allosteric regulation. (biophysics.org)
New insights into catalysis and regulation of the allosteric enzyme aspartate transcarbamoylase. (academictree.org)
2013 ) New paradigm for allosteric regulation of Escherichia coli aspartate transcarbamoylase. (academictree.org)
Allosteric regulation of protein function is a mechanism by which an event in one place of a protein structure causes an effect at another site, much like the behavior of a telecommunications network in which a collection of transmitters, receivers and transceivers communicate with each other across long distances. (montclair.edu)
In this review, conformational mobility as the common route between allosteric regulation and catalysis is discussed. (montclair.edu)
Goodey, NM & Benkovic, SJ 2008, ' Allosteric regulation and catalysis emerge via a common route ', Nature Chemical Biology , vol. 4, no. 8, pp. 474-482. (montclair.edu)
A classical model for allosteric regulation of enzyme activity posits an equilibrium between inactive and active conformations. (researcher-app.com)

When an allosteric modulator molecule -- whether natural or synthetic -- binds such a site, it changes the 3D structure of the protein, thereby affecting its function. (news-medical.net)
We report the crystal structure of the prototypic β 2 -adrenergic receptor in complex with an orthosteric agonist and compound-6FA, a positive allosteric modulator of this receptor. (harvard.edu)
Two high-resolution structures of GABAA receptors in complex with zolpidem, a positive allosteric modulator and heavily prescribed hypnotic, and DMCM, a negative allosteric modulator with convulsant and anxiogenic properties. (tcdb.org)
When cannabidiol, an allosteric modulator of CB1 , docks at the receptor, it does not initiate a signaling cascade. (projectcbd.org)
The orthosteric site is the switch that a drug turns on, whereas an allosteric modulator can either amplify or decrease a receptor's ability to transmit a signal depending on how the allosteric modulator changes the conformation of the receptor. (projectcbd.org)
A "positive allosteric modulator" changes the shape of the receptor in a way that potentiates receptor signaling, while a "negative allosteric modulator" will reduce receptor transmission. (projectcbd.org)
A site on an enzyme which upon binding of a modulator, causes the enzyme to undergo a conformational change that may alter its catalytic or binding properties. (bvsalud.org)
A solution of allopregnanolone, SAGE-547 is an intravenous allosteric modulator of both synaptic and extrasynaptic γ-aminobutyric acid type A (GABA A )receptors. (medscape.com)

The novelty and the advantages of the screening platform, the allosteric binding site addressed by these new ligands and the mechanism they use to modulate Fz4 suggest new avenues for development of inhibitors of the Wnt-β-catenin pathway and for drug discovery. (nih.gov)
We describe the mechanistic details and show that although PDK1 and Aurora kinase inhibitors bind to the conserved ATP-binding site, they differentially modulate physiological interactions at the PIF-pocket site. (pasteur.fr)
The search for therapeutics has yielded many small molecule inhibitors of the polymerase, including allosteric inhibitors that bind distal to the active site. (biophysics.org)
Understanding how allosteric inhibitors modulate the function of the HCV polymerase provides insight into what intrinsic properties of the enzyme allow it to effectively replicate viral RNA. (biophysics.org)
Our structure/function analysis of VEGFRs led to the development of novel allosteric inhibitors binding the extracellular receptor domain. (psi.ch)
However, the phosphatase is tricky to inhibit as most identified inhibitors attack the active site of the phosphatase, which is positively charged. (yalescientific.org)
To target MKP5, Bennett implemented a novel strategy: to look for inhibitors that could deactivate the enzyme without targeting the active site, also known as allosteric inhibitors. (yalescientific.org)

Thus, allosteric inhibition of MKP5 represents a therapeutic strategy against dystrophic muscle disease. (mssm.edu)
Based on this analysis we propose some relevant contact patterns and three possible binding sites which could be targeted to achieve allosteric inhibition. (sissa.it)
Candidate Binding Sites for Allosteric Inhibition of the SARS-CoV-2 Main Protease from the Analysis of Large-Scale Molecular Dynamics Simulations / Carli, M. (sissa.it)
Inhibition of RAS function through targeting an allosteric regulatory site. (iric.ca)
In theory, if not practice, allosteric modulators can prime the system for amplification or inhibition by fine-tuning receptor transmission with amazing subtlety. (projectcbd.org)

Because of this, one of the biggest efforts in drug design today aims to control enzymes without interfering with their so-called active sites -- the part of the enzyme where the biochemical reaction takes place. (news-medical.net)
Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme. (medlineplus.gov)
METHODOLOGY/PRINCIPAL FINDINGS: TsPKM has two functional domains of pyruvate kinase and the tertiary structure of TsPKM is tetramer which has the enzyme active site constituted by 8 amino-acid residues (Arg71, Asn73, Asp110, Phe241, Lys267, Glu269, Asp293 and Thr325). (bvsalud.org)
Enzymes, which are produced naturally by bacteria, cut dna molecules at specific sites denoted by base sequences when a restriction enzyme is used to cut different dna molecules, the size of the fragments generated will be unique to each molecule. (web.app)
Restriction enzyme are used to cut desired double stranded dna at specific base sequences called recognition sites to create sticky ends the plasmid is then cut by the same restriction enzyme, creating the same sticky ends as the desired donor dna. (web.app)

Allostery is a phenomenon observed in many proteins where binding of a macromolecular partner or a small-molecule ligand at one location leads to specific perturbations at a site not in direct contact with the region where the binding occurs. (pasteur.fr)
Our work outlines a strategy for developing bidirectional small-molecule allosteric modulators of protein kinases and other signaling proteins. (pasteur.fr)
Mapping major SARS-CoV-2 drug targets and assessment of druggability using computational fragment screening: Identification of an allosteric small-molecule binding site on the Nsp13 helicase. (cdc.gov)

Big Pharma has also brought to market several synthetic allosteric modulators of other receptor systems (Mimpara, Piracetam, and Selzentry, for example). (projectcbd.org)

For example, diazepam (Valium) acts on an allosteric site of the GABAA receptor in the brain, and increases its binding ability. (news-medical.net)
Its antidote, flumazenil (Lanexat), acts on the same site, but instead inhibits the receptor. (news-medical.net)
Diversity in location, mechanism, and selectivity of allosteric ligands provides potential to expand the range of receptor drugs. (harvard.edu)
In this study, we investigate the efficacy of a range of allosteric compounds using multiple GPCR readouts including arrestin recruitment, calcium mobilization, cAMP modulation and receptor internalization. (discoverx.com)
Allosteric activity was also determined for receptor internalization and provides the means to examine the effect of allosterics to alter receptor cell surface population and activation kinetics. (discoverx.com)
These structures led to the discovery of an allosteric regulatory site in the receptor ECD in subdomains 4-7. (psi.ch)
2013 ). Etomidate and propofol are potent general anesthetics that act via GABAA receptor allosteric co-agonist sites located at transmembrane beta+/alpha- inter-subunit interfaces. (tcdb.org)
Isoflurane binds to a site within the transmembrane domains of the receptor and suggest functional similarity between the GABA(A) alpha-1, -2, and -3 subunits ( Schofield and Harrison 2005 ). (tcdb.org)
THC fits snugly into a special pocket - an "orthosteric" binding site - on the CB1 receptor. (projectcbd.org)
CBD attaches to what's known as an "allosteric" binding site on the CB1 receptor. (projectcbd.org)
Allosteric modulation of CB1 changes the conformation (shape) of the receptor, and this can have a dramatic impact on the efficiency of cell signaling. (projectcbd.org)
It's not uncommon for a receptor to have two distinct binding sites or loci that can be activated by various drugs and endogenous compounds. (projectcbd.org)
Numerous pharmaceuticals target orthosteric binding sites for receptor stimulation. (projectcbd.org)
These receptor proteins are typically composed of at least two different domains: a transmembrane domain which includes the ion pore, and an extracellular domain which includes the ligand binding location (an allosteric binding site). (wikipedia.org)
[4] [5] A binding site in the extracellular N-terminal ligand-binding domain gives them receptor specificity for (1) acetylcholine (AcCh), (2) serotonin, (3) glycine, (4) glutamate and (5) γ-aminobutyric acid (GABA) in vertebrates. (wikipedia.org)
Discovery and characterization of novel subtype-selective allosteric agonists for the investigation of M(1) receptor function in the central nervous system. (vanderbilt.edu)
Targeted mutagenesis revealed a potentially novel allosteric binding site in the third extracellular loop of the M(1) receptor for these allosteric agonists. (vanderbilt.edu)
2015. Allosteric and hyperekplexic mutant phenotypes investigated on an α1 glycine receptor transmembrane structure . (ibpc.fr)
Multiple binding sites for the general anesthetic isoflurane identified in the nicotinic acetylcholine receptor transmembrane domain. (ibpc.fr)

Midazolam as a Probe for Drug-Drug Interactions Mediated by CYP3A4: Homotropic Allosteric Mechanism of Site-Specific Hydroxylation. (semanticscholar.org)
A potential clue regarding the mechanism of intersubunit communication lies in the presence of crystal structures of apo hTS in two distinct conformations of the catalytically essential active site loop ( Chen, Jansson, Sim, Larsson, & Nordlund, 2017 ). (biorxiv.org)
2012 ) Metal ion involvement in the allosteric mechanism of Escherichia coli aspartate transcarbamoylase. (academictree.org)
The mechanism of this site-to-site communication is of great interest, especially since allosteric effects must be considered in drug design and protein engineering. (montclair.edu)
Further, the ability of the three catalytic chains in the trimer to access the open and closed active-site conformations simultaneously suggests a cyclic catalytic mechanism, in which at least one of the chains is in an open conformation suitable for substrate binding whereas another chain is closed for catalytic turnover. (researcher-app.com)

Drugs targeting the orthosteric, primary binding site of G protein-coupled receptors are the most common therapeutics. (harvard.edu)
Allosteric binding sites, elsewhere on the receptors, are less well-defined, and so less exploited clinically. (harvard.edu)
Prediction of the binding-site interactions of agonists and antagonists with the receptors greatly streamlines the drug development process. (cityofhope.org)
Allosteric modulation of sigma receptors by BH3 mimetics ABT-737, ABT-263 (Navitoclax) and ABT-199 (Venetoclax). (shengsci.com)

Allosteric approaches provide opportunities for new drug discovery by overcoming ligand incompatibility with certain drug scaffolds and improving the ability of small molecules drugs to modulate peptide ligand activity. (discoverx.com)

Compounds that bind to allosteric sites offer many benefits over those which interact orthosterically. (discoverx.com)
A number of allosteric compounds have been identified in multiple disease areas including CNS (physiological and neuropathic disorders), metabolic disorder (diabetes and weight control), immunomodulation and cardiovascular indications. (discoverx.com)
Like the attraction between the north and south poles of a magnet, to attach to the positively charged site, the inhibitor compounds are often negatively charged. (yalescientific.org)

Inset: the central active site includes the C-helix and the A-loop (in red), 3 M (R95W, D117N, and R318Q), and residues important for kinase activity are depicted in the licorice representation. (nature.com)
The results show that the midazolam can be used as a sensitive probe for drug-drug interactions in human P450 CYP3A4 and mutations introduced into the F-F' loop indicate that residues F213 and D214 are directly involved in allosteric interactions leading to MDZ homotropic cooperativity. (semanticscholar.org)
This software used molecular dynamics trajectories and calculates the network of amino acid residues involved in allosteric communication between two specified sites in a protein. (cityofhope.org)
this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. (idrblab.net)

These two drugs share the extracellular benzodiazepine site at the alpha/gamma subunit interface and two transmembrane sites at beta/alpha interfaces. (tcdb.org)

In this study, we identify small molecules that bind to the ATP-binding site and affect the PIF pocket of AGC kinase family members, PDK1 and Aurora kinase. (pasteur.fr)

For example, ligand binding or an amino acid mutation at an allosteric site can alter enzymatic activity or binding affinity in a distal region such as the active site or a second binding site. (montclair.edu)

Pi limitation leads to dephosphorylation of adenosine monophosphate and the allosteric activator of isocitrate dehydrogenase key to lipid biosynthesis. (biomedcentral.com)

We solved the structure of MKP5 in complex with this inhibitor, which revealed a previously undescribed allosteric binding pocket. (mssm.edu)
Binding of the inhibitor to this pocket collapsed the MKP5 active site and was predicted to limit MAPK binding. (mssm.edu)

Positive cooperativity (sigmoidal deviation) was observed from steady state analysis of GSNOR which indicated an affinity for the binding of GSNO at this site. (uwindsor.ca)

An alternative view is that allosteric activation is achieved by increasing the potential for conformational changes that are essential for catalysis. (researcher-app.com)

Despite being clear mechanically, the two models do not capture all cases of allosteric effects, where certain proteins cannot be classified as having either hinge or shear architectures. (news-medical.net)
MEK drives BRAF activation through allosteric control of KSR proteins. (iric.ca)

Many LICs are additionally modulated by allosteric ligands , by channel blockers , ions , or the membrane potential . (wikipedia.org)

Using a functional HTS screen and subsequent diversity-oriented synthesis approach we have discovered a novel series of highly selective M(1) allosteric agonists. (vanderbilt.edu)
This series of selective M(1) allosteric agonists provides critical research tools to allow dissection of M(1)-mediated effects in the CNS and potential leads for novel treatments for Alzheimer's disease and schizophrenia. (vanderbilt.edu)

There is serious interest among drug companies in allosteric modulation of the endocannabinoid system. (projectcbd.org)

The active-site 240s loop conformation is very different between the most open and closed chains, and is disordered in the third chain, as in the holoenzyme. (researcher-app.com)

The mutations target distinct regions of RPK structure, including domain interfaces and catalytic and allosteric sites. (rcsb.org)

Despite the importance of allosteric processes, we still do not fully understand how a molecule binding on a distant and seemingly unimportant part of a large protein can change its function so dramatically. (news-medical.net)

AGC kinases have a conserved allosteric site, the phosphoinositide-dependent protein kinase 1 (PDK1)-interacting fragment (PIF) pocket, which regulates protein ATP-binding, activity, and interaction with substrates. (pasteur.fr)
Targeting undruggable carbohydrate recognition sites through focused fragment library design. (mpg.de)

Generally speaking, an allosteric drug would also be used at a comparatively lower dose than a drug acting directly on the protein's active site, thus providing more effective treatments with fewer side effects. (news-medical.net)
The catalytically active KD comprises N- and C-terminal lobes with the active site located at their interface 18 . (nature.com)
In the present study, substitution of a basic residue in the active site of the catalytic (C) trimer of aspartate transcarbamoylase with a non-polar residue results in large interdomain hinge changes in the three chains of the trimer. (researcher-app.com)
Based on the many conformations observed for the chains in the isolated catalytic trimer to date, we propose that allosteric activation of the holoenzyme occurs by release of quaternary constraint into an ensemble of active-site conformations. (researcher-app.com)

Identification of the allosteric binding site for thiazolopyrimidine on the C-type lectin langerin. (mpg.de)

The purpose of this study is to expand the mutation site of the MTHFR gene and provide genetic counseling for this family. (biomedcentral.com)

The presence of such a site was further supported by Molecular docking simulations and HDX-MS which showed that the amino acids Gly321, Lys323, Asn185 and Lys188 interact with molecules bound at this site. (uwindsor.ca)

CB1 's orthosteric binding site is also the "keyhole" for THC 's endogenous cousins, anandamide (the first endocannabinoid compound discovered in the mammalian brain) and 2AG (our most abundant endocannabinoid). (projectcbd.org)
But CBD parks at a different docking site on CB1 that is functionally distinct from THC 's orthosteric binding site. (projectcbd.org)
To extend the lock-and-key metaphor: If the orthosteric binding site is the lock on a door, then the allosteric binding site, when activated, makes the lock easier or more difficult to open. (projectcbd.org)

It consists of a pentamer of protein subunits (typically ααβγδ), with two binding sites for acetylcholine (one at the interface of each alpha subunit). (wikipedia.org)
Chapter 1 of this thesis presents a proposed allosteric binding domain on GSNOR. (uwindsor.ca)
SeeSAR automatically detects the binding site of a ligand for you. (biosolveit.de)
The oxyhemoglobin dissociation curve (see the image below) has a characteristic sigmoid shape due to the cooperative effect that exists between the multiple oxygen binding sites on the hemoglobin molecule. (medscape.com)

Restriction enzymes recognize and cut at specific places along the dna molecule called restriction sites. (web.app)

In addition, c-Src contains another central phosphorylation site that is important for kinase activity 24 , the conserved Y416 residue, which is located within the activation loop (A-loop). (nature.com)

Anatomy2

Organisms4

Chemicals and Drugs42

Analytical, Diagnostic and Therapeutic Techniques and Equipment11

Phenomena and Processes26

Disciplines and Occupations2

Information Science3

Enzyme-mononucleotide interactions: three different folds share common structural elements for ATP recognition. (1/1100)

A 20-kDa domain is required for phosphatidic acid-induced allosteric activation of phospholipase D from Streptomyces chromofuscus. (2/1100)

Stimulation of P-glycoprotein-mediated drug transport by prazosin and progesterone. Evidence for a third drug-binding site. (3/1100)

Flavodoxin: an allosteric inhibitor of AMP nucleosidase from Azotobacter vinelandii. (4/1100)

Structural elements of the gamma-aminobutyric acid type A receptor conferring subtype selectivity for benzodiazepine site ligands. (5/1100)

Metal complexes as allosteric effectors of human hemoglobin: an NMR study of the interaction of the gadolinium(III) bis(m-boroxyphenylamide)diethylenetriaminepentaacetic acid complex with human oxygenated and deoxygenated hemoglobin. (6/1100)

Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme. (7/1100)

Steric effects on multivalent ligand-receptor binding: exclusion of ligand sites by bound cell surface receptors. (8/1100)

Allosteric Site

Allosteric Regulation

Phthalimides

N-Methylscopolamine

Obidoxime Chloride

Gallamine Triethiodide

Receptor, Muscarinic M2

Phosphofructokinases

Isoindoles

Models, Molecular

Receptor, Muscarinic M1

Tacrine

Binding Sites

Kinetics

Ligands

Radioligand Assay

Glycogen Phosphorylase, Muscle Form

Protein Conformation

Protein Binding

Catalytic Domain

Adenosine Monophosphate

Fructose-Bisphosphatase

Fructosediphosphates

Crystallography, X-Ray

Molecular Structure

Protein Structure, Quaternary

CHO Cells

Protein Structure, Tertiary

Binding, Competitive

Ribonucleotide Reductases

Mutagenesis, Site-Directed

Cyclic Nucleotide Phosphodiesterases, Type 5

Hexosediphosphates

Amino Acid Sequence

Small Molecule Libraries

Receptors, Muscarinic

Structure-Activity Relationship

Cytidine Diphosphate

Cricetinae

Receptor, Muscarinic M4

Adenosine Triphosphate

Drug Discovery

Molecular Sequence Data

Cricetulus

Muscarinic Agonists

Glucose-6-Phosphate

Receptors, Metabotropic Glutamate

Affinity Labels

3',5'-Cyclic-GMP Phosphodiesterases

Carbolines

Mutation

Adenosine Diphosphate

Escherichia coli

Protein Structure, Secondary

Nicotinic Acids

Models, Chemical

Amino Acid Substitution

Enzyme Activation

Nucleotides

Drug Design

Molecular Dynamics Simulation

Substrate Specificity

Hydrogen Bonding

Uridine Triphosphate

Dimerization

Dose-Response Relationship, Drug

Piperidines

Recombinant Proteins

Magnesium

Catalysis

Receptors, G-Protein-Coupled

Drug Interactions

Models, Biological

Hydrogen-Ion Concentration

Amides

Rabbits

Cyclic GMP

Sequence Homology, Amino Acid

Aspartate Carbamoyltransferase

Disulfides