Experimental evaluation of the generalized vibrational theory of G protein-coupled receptor activation

Proceedings of the National Academy of Sciences of the United States of America
Ross D HoehnSabre Kais

Abstract

Recently, an alternative theory concerning the method by which olfactory proteins are activated has garnered attention. This theory proposes that the activation of olfactory G protein-coupled receptors occurs by an inelastic electron tunneling mechanism that is mediated through the presence of an agonist with an appropriate vibrational state to accept the inelastic portion of the tunneling electron's energy. In a recent series of papers, some suggestive theoretical evidence has been offered that this theory may be applied to nonolfactory G protein-coupled receptors (GPCRs), including those associated with the central nervous system (CNS). [Chee HK, June OS (2013) Genomics Inform 11(4):282-288; Chee HK, et al. (2015) FEBS Lett 589(4):548-552; Oh SJ (2012) Genomics Inform 10(2):128-132]. Herein, we test the viability of this idea, both by receptor affinity and receptor activation measured by calcium flux. This test was performed using a pair of well-characterized agonists for members of the 5-HT2 class of serotonin receptors, 2,5-dimethoxy-4-iodoamphetamine (DOI) and N,N-dimethyllysergamide (DAM-57), and their respective deuterated isotopologues. No evidence was found that selective deuteration affected either the binding affinit...Continue Reading

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Citations

Apr 11, 2018·Proceedings of the National Academy of Sciences of the United States of America·Lucky AhmedHanyi Zhuang
Aug 11, 2018·Proceedings of the National Academy of Sciences of the United States of America·Shu-Hao YehSabre Kais
Oct 16, 2020·Chemistry : a European Journal·Tunga SalthammerWolf-Ulrich Palm
Feb 21, 2018·ACS Chemical Neuroscience·David E Nichols
Nov 21, 2018·Journal of Agricultural and Food Chemistry·Eric Block

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