Druggable negative allosteric site of P2X3 receptors
نویسندگان
چکیده
منابع مشابه
Identification of a Negative Allosteric Site on Human α4β2 and α3β4 Neuronal Nicotinic Acetylcholine Receptors
Acetylcholine-based neurotransmission is regulated by cationic, ligand-gated ion channels called nicotinic acetylcholine receptors (nAChRs). These receptors have been linked to numerous neurological diseases and disorders such as Alzheimer's disease, Parkinson's disease, and nicotine addiction. Recently, a class of compounds has been discovered that antagonize nAChR function in an allosteric fa...
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To address the problem of specificity in G-protein coupled receptor (GPCR) drug discovery, there has been tremendous recent interest in allosteric drugs that bind at sites topographically distinct from the orthosteric site. Unfortunately, structure-based drug design of allosteric GPCR ligands has been frustrated by the paucity of structural data for allosteric binding sites, making a strong cas...
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متن کاملCooperativity of allosteric receptors.
Cooperativity of ligand binding to allosteric receptors can be quantified using the Hill coefficient (nH) to measure the sigmoidal character of the binding curve. However, for measurements of the transition between conformational states, nH values can be misleading due to ambiguity of the reference state. For cooperative ligand binding, the reference state is a hyperbolic curve for a monomer wi...
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P2X3 receptors desensitize within 100 ms of channel activation, yet recovery from desensitization requires several minutes. The molecular basis for this slow rate of recovery is unknown. We designed experiments to test the hypothesis that this slow recovery is attributable to the high affinity (< 1 nM) of desensitized P2X3 receptors for agonist. We found that agonist binding to the desensitized...
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ژورنال
عنوان ژورنال: Proceedings of the National Academy of Sciences
سال: 2018
ISSN: 0027-8424,1091-6490
DOI: 10.1073/pnas.1800907115