Disease relevance of Allosteric Site

• Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme [1].
• To identify structural factors contributing to steroid and polycyclic aromatic hydrocarbon binding to P450 enzymes and to determine the location of the allosteric site, we investigated interactions of the macrolide hydroxylase P450eryF from Saccharopolyspora erythraea with androstenedione and 9-aminophenanthrene [2].
• d-3-Phosphoglycerate dehydrogenase from Escherichia coli is a tetramer of identical subunits that is inhibited when l-serine binds at allosteric sites between subunits [3].
• This result has implicated the involvement of an arginine residue at the allosteric sites, most probably the inhibitor-binding site, of ADP-glucose pyrophosphorylase from the cyanobacterium Anabaena PCC 7120 [4].
• Affinity labelling of the allosteric site of the L-lactate dehydrogenase of Lactobacillus casei [5].

High impact information on Allosteric Site

• This effect was unrelated to the statins' inhibition of 3-hydroxy-3-methylglutaryl coenzyme-A reductase; instead it occurred via binding to a novel allosteric site within LFA-1 [6].
• Mechanistic reexamination of NO interactions with other haem proteins containing allosteric-site thiols may be warranted [7].
• A protein phosphorylation switch at the conserved allosteric site in GP [8].
• The phosphorylated threonine is buried in the allosteric site [8].
• The conductance increase gated by NMDA is potentiated by the amino acid glycine, which acts at an allosteric site tightly coupled to the NMDA receptor [9].

Chemical compound and disease context of Allosteric Site

• Gamma-aminobutyric acid (GABA) ionotropic receptor GABA(A)/benzodiazepine allosteric site is involved in both epilepsy and anxiety [10].
• Primary structure of three peptides at the catalytic and allosteric sites of the fructose-1,6-bisphosphate-activated pyruvate kinase from Escherichia coli [11].

Biological context of Allosteric Site

• A binding model is proposed in which BMS-345541 binds to similar allosteric sites on IKK-1 and IKK-2, which then affects the active sites of the subunits differently [12].
• Thus, we may conclude that fructose 2,6-bisphosphate binds to phosphofructokinase at the same allosteric site for fructose 1,6-bisphosphate while it binds to the catalytic site of fructose-1,6-bisphosphatase [13].
• Therefore, in addition to the allosteric site that binds strychnine (and probably chloromethyl brucine, another allosteric enhancer) there is a second, nonoverlapping, pharmacologically distinct allosteric site on M(3) receptors that also supports positive cooperativity with ACh [14].
• Amino acid sequence at the citrate allosteric site of rabbit muscle phosphofructokinase [15].
• Chronic treatments with drugs that stimulate or potentiate gamma-aminobutyric acid (GABA)A receptor function cause uncoupling of allosteric sites and downregulation of the GABAA receptors expressed in neurons [16].

Anatomical context of Allosteric Site

• Tetrahydroaminoacridine (THA) and a variety of other nonclassical antagonists of muscarine receptors were studied for their ability to bind to primary and allosteric sites on muscarine receptors in rabbit hippocampal membranes [17].
• Monastrol appears to inhibit microtubule-stimulated ADP release from Eg5 but does not compete with microtubule binding, suggesting that monastrol binds a novel allosteric site in the motor domain [18].
• The results suggest that edrophonium would bind to the allosteric site, resulting in the inhibition of the action of the orthosteric site of muscarinic M(3) receptors of rat trachea [19].
• These dats, together with the data obtained with microsomes (see below), support the possibility that phospholipids, in particular lysolecithin and phosphatidic acid, might function by an interaction at an allosteric site or sites to bring about a conformational change in the enzyme [20].

Associations of Allosteric Site with chemical compounds

• Stuart Forman and Keith Miller describe the physiological, biophysical and molecular biological evidence pointing to the location of a discrete allosteric site on the nicotinic acetylcholine receptor at which local anesthetics act [21].
• Data are presented which suggest that methoctramine might interact with four acidic residues of the receptor: two residues are buried in the third transmembrane segment whereas the others are located extracellularly on the loop 4-5 which may represent the allosteric site where several antagonists such as gallamine bind [22].
• In this article, Mark Robertson and colleagues propose that the properties of angiotensin AT1 receptors may be explained by a similar model, but without the need to evoke an allosteric site [23].
• The activation of these receptors by GABA can be modulated by a range of compounds acting at distinct allosteric sites [24].
• We conclude that the tyrosine kinase activity of IRs may be altered by peptide interaction at an allosteric site and, moreover, IRs require insulin to assume a conformation permitting phosphorylation by an independent kinase [25].

Gene context of Allosteric Site

• A conformational switch in the I domain allosteric site (IDAS) and in CD18 regulates LFA-1 affinity for endothelial ligands including intercellular adhesion molecule 1 (ICAM-1) [26].
• BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice [12].
• Cooperativity in transcription factor binding to the coactivator CREB-binding protein (CBP). The mixed lineage leukemia protein (MLL) activation domain binds to an allosteric site on the KIX domain [27].
• Coadministration studies of 873140 with the four other allosteric antagonists yielded data that are consistent with the notion that all five of these antagonists bind to a common allosteric site on the CCR5 receptor [28].
• It binds to a novel allosteric site that resides within the seven-transmembrane domain of mGlu5 receptors [29].

Analytical, diagnostic and therapeutic context of Allosteric Site

• GST-ASA1 cleavage by thrombin, as well as site-directed mutagenesis modifications of the Trp allosteric site, inactivated the recombinant protein [30].
• Immobilization of nucleoside diphosphatase at its allosteric site using immobilized derivatives of pyridoxal 5'-phosphate [31].

References