GPCR research has expanded in recent years from traditional orthosteric receptor-ligand interactions to encompass new approaches based on signaling via beta-arrestin, biased ligands, allosteric
ligands and persistent signaling.
The Abl enzyme controls this switching through a process called allosteric
regulation in which a part of the molecule distant from the molecules on-off switch or kinase domain somehow inhibits or activates Abl.
Among their topics are the regulation of fibroblast growth factor signaling, fibroblast growth factor in cardiovascular disease, fibroblast growth factor signaling in pulmonary hypertension, the therapeutic potential of allosteric
modulation of fibroblast growth factor receptors, fibroblast growth factors in epithelial homeostasis and repair, growth factors in the eye, and fibroblast growth factor ligand traps for treating tumors that are dependent on fibroblast growth factors.
The investigators showed further that the macrolide antibiotic clarithromycin, a negative allosteric
modulator of GABA-A receptors, reduced sleepiness in patients with central hypersomnolence syndromes in a randomized, double-blind, crossover trial (Ann Neurol.
These molecules bind to the transmembrane domain (TMD) of the FSHR and can be considered to be allosteric
The company's lead drug candidate BNC210, currently in Phase 2 for the treatment of generalized anxiety disorder, is a novel, proprietary negative allosteric
modulator of the alpha-7 nicotinic acetylcholine receptor.
In this study, we examined whether treatment of microglial cells with the mGlu4 positive allosteric
modulators (PAMs) ADX and VU813 afforded protection against lipopolysaccharide (LPS)-induced inflammatory response.
The new paper by Tonks and collaborators importantly reveals an alternative binding site, called an allosteric
site, that does not present the biochemical difficulties that the active, or "catalytic," binding site does.
Comment by allosteric
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Since CBS is normally activated by AdoMet, it is natural that the steady-state of the system is entirely influenced by this allosteric
He adds that the technique could be applied not only to protein folding intermediates, but any conformational change in proteins including allosteric
transitions and macromolecular assembly.
Thus it provides a simple and convenient method to describe both negative and positive allosteric
moderation of (biological) reaction networks.