Biochemical requirements for inhibition of Connexin26-containing channels by natural and synthetic taurine analogs.

The Journal of Biological Chemistry
Liang Tao, A L Harris

Abstract

Previous work has shown that protonated taurine and aminosulfonate pH buffers, including HEPES, can directly and reversibly inhibit connexin channels that contain connexin26 (Cx26) (Bevans, C. G., and Harris, A. L. (1999) J. Biol. Chem. 274, 3711-3719). The structural requirements for this inhibition were explored by studies of the effects of structural analogs of taurine on the activity of Cx26-containing reconstituted hemichannels from native tissue. Several analogs inhibited the channels, with a range of relative affinities and efficacies. Each active compound contains a protonated amine separated from an ionized sulfonate or sulfinate moiety by several methylene groups. The inhibition is eliminated if the sulfonate/sulfinate moiety or the amine is not present. Compounds that contain a protonated amine but lack a sulfonate/sulfinate moiety do not inhibit but do competitively block the effect of the active compounds. Compounds that lack the protonated amine do not significantly inhibit or antagonize inhibition. The results suggest involvement of the protonated amine in binding and of the ionized sulfur-containing moiety in effecting the inhibition. The maximal effect of the inhibitory compounds is enhanced when a carboxyl gro...Continue Reading

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Citations

Oct 11, 2012·The Journal of Biological Chemistry·Mariana C FioriGuillermo A Altenberg
Aug 17, 2011·The Journal of General Physiology·Darren LockeAndrew L Harris
Dec 6, 2011·Acta Crystallographica. Section C, Crystal Structure Communications·Mathias HopfingerAndreas Kornath
Aug 19, 2009·BMC Biology·Darren Locke, Andrew L Harris
Oct 19, 2011·The Journal of Physiology·Robert T R Huckstepp, Nicholas Dale
Feb 25, 2009·Journal of Structural Biology·Oliver GassmannClaudia Steinem
Nov 6, 2018·The Journal of General Physiology·Andrew L Harris
Jan 18, 2007·The Journal of Biological Chemistry·Jinshu YuGina E Sosinsky
Nov 11, 2006·Molecular Pharmacology·Liang Tao, Andrew L Harris
May 1, 2018·Frontiers in Physiology·Lina RimkuteFeliksas F Bukauskas
Jan 17, 2020·International Journal of Molecular Sciences·Camillo Peracchia
Aug 8, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Mauricio A RetamalJimmy Stehberg

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