Cooperativity between the orthosteric and allosteric ligand binding sites of RORγt
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چکیده
منابع مشابه
A novel multivalent ligand that bridges the allosteric and orthosteric binding sites of the M2 muscarinic receptor.
THRX-160209 is a potent antagonist at the M(2) muscarinic acetylcholine (ACh) receptor subtype that was designed using a multivalent strategy, simultaneously targeting the orthosteric site and a nearby site known to bind allosteric ligands. In this report, we describe three characteristics of THRX-160209 binding that are consistent with a multivalent interaction: 1) an apparent affinity of the ...
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A key question in mapping dynamics of protein-ligand interactions is to distinguish changes at binding sites from those associated with long range conformational changes upon binding at distal sites. This assumes a greater challenge when considering the interactions of low affinity ligands (dissociation constants, KD, in the μM range or lower). Amide hydrogen deuterium Exchange mass spectrometr...
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چکیده ندارد.
Identification of an allosteric binding site for RORγt inhibition
RORγt is critical for the differentiation and proliferation of Th17 cells associated with several chronic autoimmune diseases. We report the discovery of a novel allosteric binding site on the nuclear receptor RORγt. Co-crystallization of the ligand binding domain (LBD) of RORγt with a series of small-molecule antagonists demonstrates occupancy of a previously unreported allosteric binding pock...
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ژورنال
عنوان ژورنال: Proceedings of the National Academy of Sciences
سال: 2021
ISSN: 0027-8424,1091-6490
DOI: 10.1073/pnas.2021287118