Photoaffinity labeling the propofol binding site in GLIC

Biochemistry
David C ChiaraJonathan B Cohen

Abstract

Propofol, an intravenous general anesthetic, produces many of its anesthetic effects in vivo by potentiating the responses of GABA type A receptors (GABAAR), members of the superfamily of pentameric ligand-gated ion channels (pLGICs) that contain anion-selective channels. Propofol also inhibits pLGICs containing cation-selective channels, including nicotinic acetylcholine receptors and GLIC, a prokaryotic proton-gated homologue from Gloeobacter violaceus . In the structure of GLIC cocrystallized with propofol at pH 4 (presumed open/desensitized states), propofol was localized to an intrasubunit pocket at the extracellular end of the transmembrane domain within the bundle of transmembrane α-helices (Nury, H, et al. (2011) Nature 469, 428-431). To identify propofol binding sites in GLIC in solution, we used a recently developed photoreactive propofol analogue (2-isopropyl-5-[3-(trifluoromethyl)-3H-diazirin-3-yl]phenol or AziPm) that acts as an anesthetic in vivo and potentiates GABAAR in vitro. For GLIC expressed in Xenopus oocytes, propofol and AziPm inhibited current responses at pH 5.5 (EC20) with IC50 values of 20 and 50 μM, respectively. When [(3)H]AziPm (7 μM) was used to photolabel detergent-solubilized, affinity-purified ...Continue Reading

References

Feb 1, 1984·Analytical Biochemistry·A W BrauerM N Margolies
Aug 24, 2004·Nature Reviews. Neuroscience·Uwe Rudolph, Bernd Antkowiak
Feb 11, 2005·Journal of Molecular Biology·Nigel Unwin
Aug 30, 2005·Trends in Pharmacological Sciences·Hugh C HemmingsNeil L Harrison
Nov 10, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Guo-Dong LiJonathan B Cohen
Dec 15, 2006·Nature·Nicolas BocquetPierre-Jean Corringer
Jan 5, 2007·Nature·Manuel FerrerKenneth N Timmis
Feb 21, 2007·Biochemistry. Biokhimii︠a︡·E L Vodovozova
Apr 22, 2008·Nature Reviews. Neuroscience·Nicholas P Franks
Nov 26, 2009·Anesthesia and Analgesia·Yun WengJames M Sonner
Jul 6, 2010·Journal of Medicinal Chemistry·Michael A HallRoderic G Eckenhoff
Aug 18, 2010·Neuropharmacology·John E Baenziger, Pierre-Jean Corringer
Sep 23, 2010·Biophysical Journal·Qiang ChenPei Tang
Oct 28, 2011·Journal of Medicinal Chemistry·Deirdre S StewartKeith W Miller
Mar 1, 2012·Biochimica Et Biophysica Acta·Vasyl BondarenkoPei Tang
Apr 5, 2012·The Journal of Biological Chemistry·Phanindra Velisetty, Sudha Chakrapani
Jan 10, 2013·The Journal of Biological Chemistry·Selwyn S JayakarJonathan B Cohen
Jan 24, 2013·Journal of the American Chemical Society·David MowreyPei Tang
Apr 18, 2013·Nature Communications·Ludovic SauguetMarc Delarue
Sep 24, 2013·Nature Chemical Biology·Grace M S YipNicholas P Franks
Nov 22, 2013·PLoS Biology·Cosma D DellisantiCynthia Czajkowski

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Citations

Apr 1, 2014·Biochimica Et Biophysica Acta·David D MowreyPei Tang
Apr 9, 2015·Scientific Reports·Brian P WeiserRoderic G Eckenhoff
Mar 30, 2016·Structure·Benoist LaurentMarc Baaden
May 15, 2015·Alcoholism, Clinical and Experimental Research·Suzzane HoraniRebecca J Howard
Oct 16, 2014·Neuropharmacology·Stuart A FormanKeith W Miller
Oct 21, 2016·Anesthesia and Analgesia·Kellie A WollRoderic G Eckenhoff
May 10, 2017·Proceedings of the National Academy of Sciences of the United States of America·Brandon M BenselSusan P Gilbert
May 27, 2017·The Journal of Physical Chemistry. B·Ling QiuEdward J Bertaccini
Feb 16, 2018·F1000Research·Pei Tang, Roderic Eckenhoff
Mar 8, 2019·PLoS Biology·Zi-Wei ChenAlex S Evers
Jan 6, 2018·The Journal of Biological Chemistry·Wayland W L ChengAlex S Evers
Jul 19, 2018·The Journal of General Physiology·Elaine YangManuel Covarrubias
Apr 1, 2016·The Journal of Pharmacology and Experimental Therapeutics·Luvana ChowdhuryAdam C Hall
Feb 17, 2017·Molecular Neurobiology·Weiming BuManuel Covarrubias
Apr 15, 2015·Molecular Pharmacology·Ayman K HamoudaJonathan B Cohen
Dec 18, 2016·The Journal of Biological Chemistry·Zaineb FouratiMarc Delarue
Apr 11, 2018·Proceedings of the National Academy of Sciences of the United States of America·Haidai HuMarc Delarue
Jan 27, 2021·Proceedings of the National Academy of Sciences of the United States of America·Mandira DuttaBiman Jana
Jan 3, 2018·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hua-Jun Feng, Stuart A Forman
Nov 14, 2019·Biochemistry·Christopher FaulknerNora H de Leeuw

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