Shared structural mechanisms of general anaesthetics and benzodiazepines.
Allosteric Regulation
/ drug effects
Anesthetics, General
/ chemistry
Barbiturates
/ chemistry
Benzodiazepines
/ chemistry
Bicuculline
/ chemistry
Binding Sites
Binding, Competitive
/ drug effects
Cryoelectron Microscopy
Diazepam
/ chemistry
Electrophysiology
Etomidate
/ chemistry
Flumazenil
/ pharmacology
GABA-A Receptor Antagonists
/ chemistry
Humans
Ligands
Models, Molecular
Molecular Conformation
Molecular Dynamics Simulation
Phenobarbital
/ chemistry
Picrotoxin
/ chemistry
Propofol
/ chemistry
Receptors, GABA-A
/ chemistry
gamma-Aminobutyric Acid
/ chemistry
Journal
Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
20
12
2019
accepted:
01
06
2020
pubmed:
4
9
2020
medline:
18
9
2020
entrez:
4
9
2020
Statut:
ppublish
Résumé
Most general anaesthetics and classical benzodiazepine drugs act through positive modulation of γ-aminobutyric acid type A (GABA
Identifiants
pubmed: 32879488
doi: 10.1038/s41586-020-2654-5
pii: 10.1038/s41586-020-2654-5
pmc: PMC7486282
mid: NIHMS1600184
doi:
Substances chimiques
Anesthetics, General
0
Barbiturates
0
GABA-A Receptor Antagonists
0
Ligands
0
Receptors, GABA-A
0
Picrotoxin
124-87-8
Benzodiazepines
12794-10-4
Flumazenil
40P7XK9392
gamma-Aminobutyric Acid
56-12-2
Diazepam
Q3JTX2Q7TU
Bicuculline
Y37615DVKC
Propofol
YI7VU623SF
Phenobarbital
YQE403BP4D
Etomidate
Z22628B598
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
303-308Subventions
Organisme : NIDA NIH HHS
ID : R01 DA047325
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA042072
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS095899
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA037492
Pays : United States
Organisme : American Heart Association-American Stroke Association
Pays : United States
Organisme : NIGMS NIH HHS
ID : U24 GM129547
Pays : United States
Organisme : NIH HHS
ID : DA037492
Pays : United States
Organisme : NIDA NIH HHS
ID : R33 DA037492
Pays : United States
Références
Hemmings, H. C., Jr et al. Emerging molecular mechanisms of general anesthetic action. Trends Pharmacol. Sci. 26, 503–510 (2005).
pubmed: 16126282
doi: 10.1016/j.tips.2005.08.006
Forman, S. A. & Miller, K. W. Mapping general anesthetic sites in heteromeric γ-aminobutyric acid type A receptors reveals a potential for targeting receptor subtypes. Anesth. Analg. 123, 1263–1273 (2016).
pubmed: 27167687
pmcid: 5073028
doi: 10.1213/ANE.0000000000001368
Sieghart, W. & Savić, M. M. International Union of Basic and Clinical Pharmacology. CVI: GABA
pubmed: 30275042
doi: 10.1124/pr.117.014449
Sigel, E. & Ernst, M. The benzodiazepine binding sites of GABA
pubmed: 29716746
doi: 10.1016/j.tips.2018.03.006
Olsen, R. W. GABA
pubmed: 29407219
pmcid: 6027637
doi: 10.1016/j.neuropharm.2018.01.036
Meyer, H. Welche Eigenschaft der Anasthetica bedingt ihre narkotische Wirkung? Naunyn Schmiedebergs Arch. Exp. Pathol. Pharmakol. 42, 109–118 (1899).
doi: 10.1007/BF01834479
Meyer, H. Zur Theorie der Alkoholnarkose: der Einfluss wechselnder Temperatur auf Wirkungsstärke und Theilungscoefficient der Narcotica. Naunyn Schmiedebergs Arch. Exp. Pathol. Pharmakol. 46, 338–346 (1901).
doi: 10.1007/BF01978064
Overton, E. Studien über die Narkose Zugleich ein Beitrag zur allgemeinen Pharmakologie (Gustav Fischer, 1901).
Janoff, A. S., Pringle, M. J. & Miller, K. W. Correlation of general anesthetic potency with solubility in membranes. Biochim. Biophys. Acta 649, 125–128 (1981).
pubmed: 7306543
doi: 10.1016/0005-2736(81)90017-1
Franks, N. P. & Lieb, W. R. Molecular and cellular mechanisms of general anaesthesia. Nature 367, 607–614 (1994).
pubmed: 7509043
doi: 10.1038/367607a0
Krasowski, M. D. & Harrison, N. L. General anaesthetic actions on ligand-gated ion channels. Cell. Mol. Life Sci. 55, 1278–1303 (1999).
pubmed: 10487207
pmcid: 2854026
doi: 10.1007/s000180050371
Krasowski, M. D. Contradicting a unitary theory of general anesthetic action: a history of three compounds from 1901 to 2001. Bull. Anesth. Hist. 21, 1–24 (2003).
pubmed: 17494361
pmcid: 2701367
doi: 10.1016/S1522-8649(03)50031-2
Mihic, S. J. et al. Sites of alcohol and volatile anaesthetic action on GABA
pubmed: 9311780
doi: 10.1038/38738
Drexler, B., Antkowiak, B., Engin, E. & Rudolph, U. Identification and characterization of anesthetic targets by mouse molecular genetics approaches. Can. J. Anaesth. 58, 178–190 (2011).
pubmed: 21174184
doi: 10.1007/s12630-010-9414-1
Walters, R. J., Hadley, S. H., Morris, K. D. & Amin, J. Benzodiazepines act on GABA
pubmed: 11100148
doi: 10.1038/81800
Middendorp, S. J., Maldifassi, M. C., Baur, R. & Sigel, E. Positive modulation of synaptic and extrasynaptic GABA
pubmed: 25963418
doi: 10.1016/j.neuropharm.2015.04.027
Votey, S. R., Bosse, G. M., Bayer, M. J. & Hoffman, J. R. Flumazenil: a new benzodiazepine antagonist. Ann. Emerg. Med. 20, 181–188 (1991).
pubmed: 1996802
doi: 10.1016/S0196-0644(05)81219-3
Laverty, D. et al. Cryo-EM structure of the human α1β3γ2 GABA
pubmed: 30602789
doi: 10.1038/s41586-018-0833-4
Masiulis, S. et al. GABA
pubmed: 30602790
pmcid: 6370056
doi: 10.1038/s41586-018-0832-5
Löscher, W. & Rogawski, M. A. How theories evolved concerning the mechanism of action of barbiturates. Epilepsia 53, 12–25 (2012).
pubmed: 23205959
doi: 10.1111/epi.12025
Zhu, S. et al. Structure of a human synaptic GABA
pubmed: 29950725
pmcid: 6220708
doi: 10.1038/s41586-018-0255-3
Gielen, M., Barilone, N. & Corringer, P.-J. The desensitization pathway of GABA
Chiara, D. C. et al. Specificity of intersubunit general anesthetic-binding sites in the transmembrane domain of the human α1β3γ2 γ-aminobutyric acid type A (GABA
pubmed: 23677991
pmcid: 3707639
doi: 10.1074/jbc.M113.479725
Zeller, A., Arras, M., Jurd, R. & Rudolph, U. Identification of a molecular target mediating the general anesthetic actions of pentobarbital. Mol. Pharmacol. 71, 852–859 (2007).
pubmed: 17164405
doi: 10.1124/mol.106.030049
Belelli, D., Callachan, H., Hill-Venning, C., Peters, J. A. & Lambert, J. J. Interaction of positive allosteric modulators with human and Drosophila recombinant GABA receptors expressed in Xenopus laevis oocytes. Br. J. Pharmacol. 118, 563–576 (1996).
pubmed: 8762079
pmcid: 1909744
doi: 10.1111/j.1476-5381.1996.tb15439.x
Vuyk, J., Sitsen, E. & Reekers, M. in Miller’s Anesthesia 9th edn (eds Gropper, M. A. et al.) Ch. 23, 638–679 (Elsevier, 2020).
Forman, S. A. Clinical and molecular pharmacology of etomidate. Anesthesiology 114, 695–707 (2011).
pubmed: 21263301
doi: 10.1097/ALN.0b013e3181ff72b5
Belelli, D., Lambert, J. J., Peters, J. A., Wafford, K. & Whiting, P. J. The interaction of the general anesthetic etomidate with the γ-aminobutyric acid type A receptor is influenced by a single amino acid. Proc. Natl Acad. Sci. USA 94, 11031–11036 (1997).
pubmed: 9380754
doi: 10.1073/pnas.94.20.11031
pmcid: 23576
Siegwart, R., Jurd, R. & Rudolph, U. Molecular determinants for the action of general anesthetics at recombinant α
pubmed: 11796752
doi: 10.1046/j.0022-3042.2001.00682.x
Li, G. D. et al. Identification of a GABA
pubmed: 17093081
pmcid: 6674783
doi: 10.1523/JNEUROSCI.3467-06.2006
Krasowski, M. D. et al. Propofol and other intravenous anesthetics have sites of action on the γ-aminobutyric acid type A receptor distinct from that for isoflurane. Mol. Pharmacol. 53, 530–538 (1998).
pubmed: 9495821
doi: 10.1124/mol.53.3.530
Jayakar, S. S. et al. Multiple propofol-binding sites in a γ-aminobutyric acid type A receptor (GABA
pubmed: 25086038
pmcid: 4183786
doi: 10.1074/jbc.M114.581728
Bali, M. & Akabas, M. H. Gating-induced conformational rearrangement of the γ-aminobutyric acid type A receptor β-α subunit interface in the membrane-spanning domain. J. Biol. Chem. 287, 27762–27770 (2012).
pubmed: 22730325
pmcid: 3431678
doi: 10.1074/jbc.M112.363341
Jayakar, S. S. et al. Identifying drugs that bind selectively to intersubunit general anesthetic sites in the α1β3γ2 GABA
pubmed: 30952799
pmcid: 6505378
doi: 10.1124/mol.118.114975
Yip, G. M. et al. A propofol binding site on mammalian GABA
pubmed: 24056400
pmcid: 3951778
doi: 10.1038/nchembio.1340
Jurd, R. et al. General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA
pubmed: 12475885
doi: 10.1096/fj.02-0611fje
Reynolds, D. S. et al. Sedation and anesthesia mediated by distinct GABA
pubmed: 13679430
pmcid: 6740367
doi: 10.1523/JNEUROSCI.23-24-08608.2003
Chiara, D. C. et al. Mapping general anesthetic binding site(s) in human α1β3 γ-aminobutyric acid type A receptors with [
pubmed: 22243422
doi: 10.1021/bi201772m
Krasowski, M. D., Hong, X., Hopfinger, A. J. & Harrison, N. L. 4D-QSAR analysis of a set of propofol analogues: mapping binding sites for an anesthetic phenol on the GABA
pubmed: 12109905
pmcid: 2864546
doi: 10.1021/jm010461a
Krasowski, M. D., Nishikawa, K., Nikolaeva, N., Lin, A. & Harrison, N. L. Methionine 286 in transmembrane domain 3 of the GABA
pubmed: 11747900
pmcid: 2855216
doi: 10.1016/S0028-3908(01)00141-1
Eaton, M. M. et al. Multiple non-equivalent interfaces mediate direct activation of GABA
pubmed: 26830963
pmcid: 5050400
doi: 10.2174/1570159X14666160202121319
Ritchie, T. K. et al. Chapter eleven - reconstitution of membrane proteins in phospholipid bilayer nanodiscs. Methods Enzymol. 464, 211–231 (2009).
pubmed: 19903557
pmcid: 4196316
doi: 10.1016/S0076-6879(09)64011-8
Damgen, M. A. & Biggin, P. C. A refined open state of the glycine receptor obtained via molecular dynamics simulations. Structure 28, 130–139.e2 (2020).
pubmed: 31753620
pmcid: 6945115
doi: 10.1016/j.str.2019.10.019
Gielen, M., Thomas, P. & Smart, T. G. The desensitization gate of inhibitory Cys-loop receptors. Nat. Commun. 6, 6829 (2015).
pubmed: 25891813
doi: 10.1038/ncomms7829
Dahaba, A. A. et al. Effect of flumazenil on bispectral index monitoring in unpremedicated patients. Anesthesiology 110, 1036–1040 (2009).
pubmed: 19352163
doi: 10.1097/ALN.0b013e31819db2c4
Safavynia, S. A. et al. Effects of γ-aminobutyric acid type A receptor modulation by flumazenil on emergence from general anesthesia. Anesthesiology 125, 147–158 (2016).
pubmed: 27111534
doi: 10.1097/ALN.0000000000001134
Ueno, S., Bracamontes, J., Zorumski, C., Weiss, D. S. & Steinbach, J. H. Bicuculline and gabazine are allosteric inhibitors of channel opening of the GABA
pubmed: 8987785
pmcid: 6573228
doi: 10.1523/JNEUROSCI.17-02-00625.1997
Baumann, S. W., Baur, R. & Sigel, E. Individual properties of the two functional agonist sites in GABA
pubmed: 14657175
pmcid: 6741049
doi: 10.1523/JNEUROSCI.23-35-11158.2003
Rosen, A., Bali, M., Horenstein, J. & Akabas, M. H. Channel opening by anesthetics and GABA induces similar changes in the GABA
pubmed: 17293408
pmcid: 1852347
doi: 10.1529/biophysj.106.094490
Kim, J. H. et al. High cleavage efficiency of a 2Å peptide derived from porcine teschovirus-1 in human cell lines, zebrafish and mice. PLoS ONE 6, e18556 (2011).
pubmed: 21602908
pmcid: 3084703
doi: 10.1371/journal.pone.0018556
Morales-Perez, C. L., Noviello, C. M. & Hibbs, R. E. Manipulation of subunit stoichiometry in heteromeric membrane proteins. Structure 24, 797–805 (2016).
pubmed: 27041595
pmcid: 4856541
doi: 10.1016/j.str.2016.03.004
Lyons, J. A., Bøggild, A., Nissen, P. & Frauenfeld, J. Chapter three - saposin–lipoprotein scaffolds for structure determination of membrane transporters. Methods Enzymol. 594, 85–99 (2017).
pubmed: 28779844
doi: 10.1016/bs.mie.2017.06.035
Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).
pubmed: 30412051
pmcid: 6250425
Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).
pubmed: 28250466
pmcid: 5494038
doi: 10.1038/nmeth.4193
Zhang, K. Gctf: real-time CTF determination and correction. J. Struct. Biol. 193, 1–12 (2016).
pubmed: 26592709
pmcid: 4711343
Rohou, A. & Grigorieff, N. CTFFIND4: Fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216–221 (2015).
pubmed: 26278980
pmcid: 6760662
doi: 10.1016/j.jsb.2015.08.008
Wagner, T. et al. SPHIRE-crYOLO is a fast and accurate fully automated particle picker for cryo-EM. Commun. Biol. 2, 218 (2019).
pubmed: 31240256
pmcid: 6584505
doi: 10.1038/s42003-019-0437-z
Bai, X. C., Rajendra, E., Yang, G., Shi, Y. & Scheres, S. H. Sampling the conformational space of the catalytic subunit of human γ-secretase. eLife 4, e11182 (2015).
pubmed: 26623517
pmcid: 4718806
doi: 10.7554/eLife.11182
Kucukelbir, A., Sigworth, F. J. & Tagare, H. D. Quantifying the local resolution of cryo-EM density maps. Nat. Methods 11, 63–65 (2014).
pubmed: 24213166
doi: 10.1038/nmeth.2727
Schwede, T., Kopp, J., Guex, N. & Peitsch, M. C. SWISS-MODEL: an automated protein homology-modeling server. Nucleic Acids Res. 31, 3381–3385 (2003).
pubmed: 12824332
pmcid: 168927
doi: 10.1093/nar/gkg520
Miller, P. S. & Aricescu, A. R. Crystal structure of a human GABA
pubmed: 24909990
pmcid: 4167603
doi: 10.1038/nature13293
Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
pubmed: 15264254
doi: 10.1002/jcc.20084
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010).
pubmed: 20383002
doi: 10.1107/S0907444910007493
pmcid: 2852313
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213–221 (2010).
Laskowski, R. A. & Swindells, M. B. LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. J. Chem. Inf. Model. 51, 2778–2786 (2011).
pubmed: 21919503
doi: 10.1021/ci200227u
Krissinel, E. & Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774–797 (2007).
pubmed: 17681537
doi: 10.1016/j.jmb.2007.05.022
Smart, O. S., Neduvelil, J. G., Wang, X., Wallace, B. A. & Sansom, M. S. HOLE: a program for the analysis of the pore dimensions of ion channel structural models. J. Mol. Graph. 14, 354–360 (1996).
pubmed: 9195488
doi: 10.1016/S0263-7855(97)00009-X
Pei, J., Kim, B. H. & Grishin, N. V. PROMALS3D: a tool for multiple protein sequence and structure alignments. Nucleic Acids Res. 36, 2295–2300 (2008).
pubmed: 18287115
pmcid: 2367709
doi: 10.1093/nar/gkn072
Morin, A. et al. Collaboration gets the most out of software. eLife 2, e01456 (2013).
pubmed: 24040512
pmcid: 3771563
doi: 10.7554/eLife.01456
Jo, S., Kim, T., Iyer, V. G. & Im, W. CHARMM-GUI: a web-based graphical user interface for CHARMM. J. Comput. Chem. 29, 1859–1865 (2008).
pubmed: 18351591
doi: 10.1002/jcc.20945
Abraham, M. J. et al. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1–2, 19–25 (2015).
doi: 10.1016/j.softx.2015.06.001
Periole, X. & Marrink, S. J. The Martini coarse-grained force field. Methods Mol. Biol. 924, 533–565 (2013).
pubmed: 23034762
doi: 10.1007/978-1-62703-017-5_20
Wassenaar, T. A., Pluhackova, K., Böckmann, R. A., Marrink, S. J. & Tieleman, D. P. Going backward: a flexible geometric approach to reverse transformation from coarse grained to atomistic models. J. Chem. Theory Comput. 10, 676–690 (2014).
pubmed: 26580045
doi: 10.1021/ct400617g
Best, R. B. et al. Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ
pubmed: 23341755
pmcid: 3549273
doi: 10.1021/ct300400x
Vanommeslaeghe, K. et al. CHARMM general force field: a force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J. Comput. Chem. 31, 671–690 (2010).
pubmed: 19575467
pmcid: 2888302
Bussi, G., Donadio, D. & Parrinello, M. Canonical sampling through velocity rescaling. J. Chem. Phys. 126, 014101 (2007).
pubmed: 17212484
doi: 10.1063/1.2408420
Parrinello, M. & Rahman, A. Crystal structure and pair potentials: a molecular-dynamics study. Phys. Rev. Lett. 45, 1196–1199 (1980).
doi: 10.1103/PhysRevLett.45.1196
Essmann, U. et al. A smooth particle mesh Ewald method. J. Chem. Phys. 103, 8577–8593 (1995).
doi: 10.1063/1.470117
Hess, B. P-LINCS: a parallel linear constraint solver for molecular simulation. J. Chem. Theory Comput. 4, 116–122 (2008).
pubmed: 26619985
doi: 10.1021/ct700200b
Humphrey, W., Dalke, A. & Schulten, K. VMD: visual molecular dynamics. J. Mol. Graph. 14, 33–38 (1996).
pubmed: 8744570
doi: 10.1016/0263-7855(96)00018-5
Michaud-Agrawal, N., Denning, E. J., Woolf, T. B. & Beckstein, O. MDAnalysis: a toolkit for the analysis of molecular dynamics simulations. J. Comput. Chem. 32, 2319–2327 (2011).
pubmed: 21500218
pmcid: 3144279
doi: 10.1002/jcc.21787
McGibbon, R. T. et al. MDTraj: a modern open library for the analysis of molecular dynamics trajectories. Biophys. J. 109, 1528–1532 (2015).
pubmed: 26488642
pmcid: 4623899
doi: 10.1016/j.bpj.2015.08.015
Orellana, L., Yoluk, O., Carrillo, O., Orozco, M. & Lindahl, E. Prediction and validation of protein intermediate states from structurally rich ensembles and coarse-grained simulations. Nat. Commun. 7, 12575 (2016).
pubmed: 27578633
pmcid: 5013691
doi: 10.1038/ncomms12575
Lindahl, V., Gourdon, P., Andersson, M. & Hess, B. Permeability and ammonia selectivity in aquaporin TIP2;1: linking structure to function. Sci. Rep. 8, 2995 (2018).
pubmed: 29445244
pmcid: 5813003
doi: 10.1038/s41598-018-21357-2
Phulera, S. et al. Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABA
pubmed: 30044221
pmcid: 6086659
doi: 10.7554/eLife.39383
Miller, P. S. et al. Heteromeric GABA
Ingólfsson, H. I. et al. Computational lipidomics of the neuronal plasma membrane. Biophys. J. 113, 2271–2280 (2017).
pubmed: 29113676
pmcid: 5700369
doi: 10.1016/j.bpj.2017.10.017
Nury, H. et al. X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel. Nature 469, 428–431 (2011).
pubmed: 21248852
doi: 10.1038/nature09647
Fourati, Z. et al. Structural basis for a bimodal allosteric mechanism of general anesthetic modulation in pentameric ligand-gated ion channels. Cell Rep. 23, 993–1004 (2018).
pubmed: 29694907
doi: 10.1016/j.celrep.2018.03.108
Hibbs, R. E. & Gouaux, E. Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474, 54–60 (2011).
pubmed: 21572436
pmcid: 3160419
doi: 10.1038/nature10139