Erwin Sigel

Summary

Affiliation: University of Bern
Country: Switzerland

Publications

  1. pmc Influence of GABA(A) receptor α subunit isoforms on the benzodiazepine binding site
    Benjamin P Lüscher
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
    PLoS ONE 7:e42101. 2012
  2. pmc Structure, function, and modulation of GABA(A) receptors
    Erwin Sigel
    Institute of Biochemistry and Molecular Medicine, University of Bern, CH 3012 Bern, Switzerland
    J Biol Chem 287:40224-31. 2012
  3. doi request reprint Relative positioning of diazepam in the benzodiazepine-binding-pocket of GABA receptors
    Kelly R Tan
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse, Switzerland
    J Neurochem 111:1264-73. 2009
  4. doi request reprint Covalent modification of GABAA receptor isoforms by a diazepam analogue provides evidence for a novel benzodiazepine binding site that prevents modulation by these drugs
    Roland Baur
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
    J Neurochem 106:2353-63. 2008
  5. ncbi request reprint On the benzodiazepine binding pocket in GABAA receptors
    Dmytro Berezhnoy
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    J Biol Chem 279:3160-8. 2004
  6. doi request reprint Structure of alpha6 beta3 delta GABA(A) receptors and their lack of ethanol sensitivity
    Roland Baur
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
    J Neurochem 111:1172-81. 2009
  7. ncbi request reprint Individual properties of the two functional agonist sites in GABA(A) receptors
    Sabine W Baumann
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    J Neurosci 23:11158-66. 2003
  8. ncbi request reprint Proximity-accelerated chemical coupling reaction in the benzodiazepine-binding site of gamma-aminobutyric acid type A receptors: superposition of different allosteric modulators
    Kelly R Tan
    Institute of Biochemistry and Molecular Medicine, University of Bern, Buhlstrasse 28, Bern CH 3012, Switzerland
    J Biol Chem 282:26316-25. 2007
  9. ncbi request reprint Consequence of the presence of two different beta subunit isoforms in a GABA(A) receptor
    Nathalie Boulineau
    Department of Pharmacology, University of Bern, Bern, Switzerland
    J Neurochem 95:1724-31. 2005
  10. doi request reprint Molecular analysis of the site for 2-arachidonylglycerol (2-AG) on the β₂ subunit of GABA(A) receptors
    Roland Baur
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
    J Neurochem 126:29-36. 2013

Collaborators

Detail Information

Publications35

  1. pmc Influence of GABA(A) receptor α subunit isoforms on the benzodiazepine binding site
    Benjamin P Lüscher
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
    PLoS ONE 7:e42101. 2012
    ....
  2. pmc Structure, function, and modulation of GABA(A) receptors
    Erwin Sigel
    Institute of Biochemistry and Molecular Medicine, University of Bern, CH 3012 Bern, Switzerland
    J Biol Chem 287:40224-31. 2012
    ..GABA(A) receptors are responsive to a wide variety of drugs, e.g. benzodiazepines, which are often used for their sedative/hypnotic and anxiolytic effects...
  3. doi request reprint Relative positioning of diazepam in the benzodiazepine-binding-pocket of GABA receptors
    Kelly R Tan
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse, Switzerland
    J Neurochem 111:1264-73. 2009
    ..Based on these observations we propose a relative positioning of diazepam within the benzodiazepine-binding site of alpha(1)beta(2)gamma(2) receptors...
  4. doi request reprint Covalent modification of GABAA receptor isoforms by a diazepam analogue provides evidence for a novel benzodiazepine binding site that prevents modulation by these drugs
    Roland Baur
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
    J Neurochem 106:2353-63. 2008
    ..Our results indicate that this site may be located at the alpha/beta subunit interface pseudo-symmetrically to the site for classical benzodiazepines located at the alpha/gamma interface...
  5. ncbi request reprint On the benzodiazepine binding pocket in GABAA receptors
    Dmytro Berezhnoy
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    J Biol Chem 279:3160-8. 2004
    ..We present in addition evidence that gamma(2)Ala-79 is probably located in the access pathway of the ligand to its binding pocket...
  6. doi request reprint Structure of alpha6 beta3 delta GABA(A) receptors and their lack of ethanol sensitivity
    Roland Baur
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
    J Neurochem 111:1172-81. 2009
    ..We conclude from the investigated receptors that the delta subunit can assume multiple positions in a receptor pentamer composed of alpha(6), beta(3) and delta subunits...
  7. ncbi request reprint Individual properties of the two functional agonist sites in GABA(A) receptors
    Sabine W Baumann
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    J Neurosci 23:11158-66. 2003
    ....
  8. ncbi request reprint Proximity-accelerated chemical coupling reaction in the benzodiazepine-binding site of gamma-aminobutyric acid type A receptors: superposition of different allosteric modulators
    Kelly R Tan
    Institute of Biochemistry and Molecular Medicine, University of Bern, Buhlstrasse 28, Bern CH 3012, Switzerland
    J Biol Chem 282:26316-25. 2007
    ..Taken together with previous data, a similar orientation of these ligands within the benzodiazepine-binding pocket may be proposed...
  9. ncbi request reprint Consequence of the presence of two different beta subunit isoforms in a GABA(A) receptor
    Nathalie Boulineau
    Department of Pharmacology, University of Bern, Bern, Switzerland
    J Neurochem 95:1724-31. 2005
    ....
  10. doi request reprint Molecular analysis of the site for 2-arachidonylglycerol (2-AG) on the β₂ subunit of GABA(A) receptors
    Roland Baur
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
    J Neurochem 126:29-36. 2013
    ..The influence of the structure of the head group of the ligand molecule on the activity of the molecule was also investigated. We present a model of 2-AG docked to the GABA(A) receptor...
  11. ncbi request reprint A closer look at the high affinity benzodiazepine binding site on GABAA receptors
    Erwin Sigel
    Department of Biochemistry and Molecular Medicine, University of Bern, Buehlstrasse 28, Bern, Switzerland
    Curr Top Med Chem 11:241-6. 2011
    ..We also discuss a newly postulated modulatory site for benzodiazepines at the α(1)/β(2) subunit interface, homologous to the classical benzodiazepine binding pocket...
  12. ncbi request reprint Influence of the point mutation alpha-1-H101R on the assembly of gamma-aminobutyric acid type A receptors
    Roland Baur
    Department of Pharmacology, University of Bern, Bern, Switzerland
    Neuroreport 16:1955-8. 2005
    ..Here, we investigated the assembly properties of mutated in comparison with wild-type subunits, and demonstrate that alpha1H101R has similar assembly properties as wild-type alpha1...
  13. ncbi request reprint Two neighboring residues of loop A of the alpha1 subunit point towards the benzodiazepine binding site of GABAA receptors
    Kelly R Tan
    Institute of Biochemistry and Molecular Medicine, University of Bern, Buhlstrasse 28, CH 3012 Bern, Switzerland
    FEBS Lett 581:4718-22. 2007
    ..We describe a direct interaction of alpha(1)N102 with a diazepam- and an imidazobenzodiazepine-derivative. Our observations help to better understand the conformation of this region of the benzodiazepine pocket in GABA(A) receptor...
  14. ncbi request reprint Conformational changes at benzodiazepine binding sites of GABA(A) receptors detected with a novel technique
    Dmytro Berezhnoy
    Department of Pharmacology, University of Bern, Bern, Switzerland
    J Neurochem 92:859-66. 2005
    ..It is concluded that Ro15-1788 efficiently protects activated and desensitized states, but not the resting state...
  15. pmc Diversity of structure and function of alpha1alpha6beta3delta GABAA receptors: comparison with alpha1beta3delta and alpha6beta3delta receptors
    Roland Baur
    Institute of Biochemistry and Molecular Medicine, University of Bern, CH 3012 Bern, Switzerland
    J Biol Chem 285:17398-405. 2010
    ..This property is shared by alpha(1)beta(3)delta and alpha(6)beta(3)delta receptors, but there are differences in the additionally expressed isoforms...
  16. pmc Unanticipated structural and functional properties of delta-subunit-containing GABAA receptors
    Kuldeep H Kaur
    Institute of Biochemistry and Molecular Medicine, University of Bern, CH 3012 Bern, Switzerland
    J Biol Chem 284:7889-96. 2009
    ..Furthermore, we show that the delta-subunit can contribute to the formation of an agonist site in alpha(1)-beta(3)-alpha(1)/beta(3)-delta receptors...
  17. ncbi request reprint A GABA(A) receptor of defined subunit composition and positioning: concatenation of five subunits
    Roland Baur
    Department of Pharmacology, University of Bern, Friedbuhlstrasse 49, CH 3010 Bern, Switzerland
    FEBS Lett 580:1616-20. 2006
    ..The ability to express receptors consisting of five subunits enables detailed studies of GABA(A) receptor subtype selective compounds...
  18. doi request reprint Use of concatamers to study GABAA receptor architecture and function: application to delta-subunit-containing receptors and possible pitfalls
    Erwin Sigel
    Institute of Biochemistry and Molecular Medicine, University of Bern, CH 3012 Bern, Switzerland
    Biochem Soc Trans 37:1338-42. 2009
    ..As some concatenated constructs result by themselves in a low level of expression, this erroneous assembly leading to receptor function may be promoted by overloading the expression system and leads to wrong conclusions...
  19. ncbi request reprint On high- and low-affinity agonist sites in GABAA receptors
    Roland Baur
    Department of Pharmacology, University of Bern, Bern, Switzerland
    J Neurochem 87:325-32. 2003
    ..Our observations are relevant for the relative location of high- and low-affinity agonist sites in GABAA receptors...
  20. ncbi request reprint Novel plant substances acting as beta subunit isoform-selective positive allosteric modulators of GABAA receptors
    Roland Baur
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    Mol Pharmacol 68:787-92. 2005
    ..In summary, these positive allosteric modulators of GABAA receptors of plant origin have a novel unusual chemical structure and act at a site independent of that of benzodiazepines and loreclezole...
  21. ncbi request reprint The Xenopus oocyte: system for the study of functional expression and modulation of proteins
    Erwin Sigel
    Department of Pharmacology, University of Bern, Bern, Switzerland
    Mol Nutr Food Res 49:228-34. 2005
  22. doi request reprint Monepantel allosterically activates DEG-3/DES-2 channels of the gastrointestinal nematode Haemonchus contortus
    Lucien Rufener
    Institute of Cell Biology, University of Bern, Buhlstrasse 28, CH 3012 Bern, Switzerland
    Mol Pharmacol 78:895-902. 2010
    ..contortus DEG-3/DES-2 receptors with choline. In summary, we present the first direct evidence for interaction of AADs with DEG-3-type acetylcholine receptors and discuss these findings in the context of anthelmintic action of AADs...
  23. doi request reprint Replacement of histidine in position 105 in the α₅ subunit by cysteine stimulates zolpidem sensitivity of α₅β₂γ₂ GABA(A) receptors
    Roland Baur
    Department of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
    J Neurochem 103:2556-64. 2007
    ..Thus, the nature of the amino acid residue in this position is not only crucial for the action of classical benzodiazepines but in α(5) containing receptors also for the action of zolpidem...
  24. doi request reprint Characterization of choline uptake in Trypanosoma brucei procyclic and bloodstream forms
    Juan P Macedo
    Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland
    Mol Biochem Parasitol 190:16-22. 2013
    ..Together, our results show that T. brucei parasites express an uptake system for choline and that exogenous choline is used for PC synthesis. ..
  25. ncbi request reprint Functional characterization of the new human GABA(A) receptor mutation beta3(R192H)
    Andreas Buhr
    Department of Pharmacology, University of Bern, Friedbuehlstrasse 49, CH 3010 Bern, Switzerland
    Hum Genet 111:154-60. 2002
    ..The mutation beta3(R192H) might, therefore, be linked to this condition. The intron/exon boundaries of the alpha1 subunit gene were also established and three additional variants were found in the alpha1 and beta3 genes...
  26. doi request reprint A residue close to α1 loop F disrupts modulation of GABAA receptors by benzodiazepines while their binding is maintained
    Roland Baur
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
    J Neurochem 115:1478-85. 2010
    ..We infer that also broader regions could contribute to signaling from GABA agonist binding to channel opening...
  27. ncbi request reprint Mapping of the benzodiazepine recognition site on GABA(A) receptors
    Erwin Sigel
    Department of Pharmacology, University of Bern, Bern, Switzerland
    Curr Top Med Chem 2:833-9. 2002
    ....
  28. pmc myo-Inositol uptake is essential for bulk inositol phospholipid but not glycosylphosphatidylinositol synthesis in Trypanosoma brucei
    Amaia González-Salgado
    Institute of Biochemistry and Molecular Medicine, University of Bern, Buhlstrasse 28, 3012 Bern, Switzerland
    J Biol Chem 287:13313-23. 2012
    ..This together with the unexpected localization of the myo-inositol transporter in both the plasma membrane and the Golgi demonstrate that metabolism of endogenous and exogenous myo-inositol in T. brucei is strictly segregated...
  29. ncbi request reprint Techniques: Use of concatenated subunits for the study of ligand-gated ion channels
    Frédéric Minier
    Department of Pharmacology, University of Bern, Friedbühlstr 49, CH 3010 Bern, Switzerland
    Trends Pharmacol Sci 25:499-503. 2004
    ..Thus, this method also facilitates the investigation of positional effects of mutations associated with diseases...
  30. pmc Positioning of the alpha-subunit isoforms confers a functional signature to gamma-aminobutyric acid type A receptors
    Frédéric Minier
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    Proc Natl Acad Sci U S A 101:7769-74. 2004
    ..This method may also be applied to the study of other ion channels...
  31. pmc A venom-derived neurotoxin, CsTx-1, from the spider Cupiennius salei exhibits cytolytic activities
    Lucia Kuhn-Nentwig
    Institute of Ecology and Evolution, University of Bern, Baltzerstrasse 6, CH 3012 Bern, Switzerland
    J Biol Chem 287:25640-9. 2012
    ..Such a dualism is discussed as an important new mechanism for the evolution of spider venomous peptides...
  32. ncbi request reprint Forced subunit assembly in alpha1beta2gamma2 GABAA receptors. Insight into the absolute arrangement
    Sabine W Baumann
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    J Biol Chem 277:46020-5. 2002
    ..The methods established here should be applicable to the entire ion channel family comprising nicotinic acetylcholine, glycine, and 5HT(3) receptors...
  33. pmc The major central endocannabinoid directly acts at GABA(A) receptors
    Erwin Sigel
    Institute of Biochemistry and Molecular Medicine, University of Bern, CH 3012 Bern, Switzerland
    Proc Natl Acad Sci U S A 108:18150-5. 2011
    ..The identification of a functional binding site for 2-AG in the GABA(A) receptor may have far-reaching consequences for the study of locomotion and sedation...
  34. doi request reprint Anticipating antiport in P-type ATPases
    Verena Niggli
    Institute of Pathology, University of Bern, Murtenstrasse 31, Bern, Switzerland
    Trends Biochem Sci 33:156-60. 2008
    ..New data based on the crystal structure of SERCA now strongly indicate that countertransport could be mandatory for all P-type ATPases. This concept should be verified for other known and for all newly characterized P-type ATPases...