Mutations at beta N265 in c-aminobutyric acid type a receptors alter both binding affinity and efficacy of potent anesthetics

PLoS ONE

Volumn 9, Issue 10, 2014, Pages

  Stewart, Deirdre S ^a   Pierce, David W ^a   Hotta, Mayo ^a,b   Stern, Alex T ^a   Forman, Stuart A ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID A RECEPTOR; ETOMIDATE; GLUTAMINE; METHIONINE; PROLINE; PROPOFOL; INTRAVENOUS ANESTHETIC AGENT; PROTEIN BINDING;

ADULT; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CHANNEL GATING; DRUG BINDING SITE; DRUG EFFECT; DRUG EFFICACY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SENSITIVITY; FEMALE; GENE MUTATION; HETEROLOGOUS EXPRESSION; MUTANT; NONHUMAN; OOCYTE; PROTEIN MODIFICATION; REPORTER GENE; VOLTAGE CLAMP TECHNIQUE; XENOPUS LAEVIS; AMINO ACID SEQUENCE; ANIMAL; CHEMISTRY; GENETICS; HUMAN; METABOLISM; MISSENSE MUTATION; MOLECULAR GENETICS; PROTEIN TERTIARY STRUCTURE; XENOPUS;

AMINO ACID SEQUENCE; ANESTHETICS, INTRAVENOUS; ANIMALS; ETOMIDATE; HUMANS; MOLECULAR SEQUENCE DATA; MUTATION, MISSENSE; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, GABA-A; XENOPUS;

EID: 84908583791     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0111470     Document Type: Article

References (55)

1. Rüsch D, Zhong H, Forman SA (2004) Gating allosterism at a single class of etomidate sites on alpha1beta2gamma2L GABA-A receptors accounts for both direct activation and agonist modulation. J Biol Chem 279: 20982-20992.
2. Rüsch D, Neumann E, Wulf H, Forman SA (2012) An Allosteric Coagonist Model for Propofol Effects on alpha1beta2gamma2L gamma-Aminobutyric Acid Type A Receptors. Anesthesiology 116: 47-55.
3. Zeller A, Arras M, Jurd R, Rudolph U (2007) Mapping the contribution of beta3-containing GABAA receptors to volatile and intravenous general anesthetic actions. BMC Pharmacol 7: 2.
4. Olsen RW, Sieghart W (2008) International Union of Pharmacology. LXX. Subtypes of gamma-aminobutyric acid(A) receptors: Classification on the basis of subunit composition, pharmacology, and function. Pharmacol Rev 60: 243-260.
5. Corringer PJ, Poitevin F, Prevost MS, Sauguet L, Delarue M, et al. (2012) Structure and pharmacology of pentameric receptor channels: from bacteria to brain. Structure 20: 941-956.
6. Baumann SW, Baur R, Sigel E (2002) Forced subunit assembly in alpha1beta2gamma2 GABAA receptors. Insight into the absolute arrangement. J Biol Chem 277: 46020-46025.
7. Miller PS, Aricescu AR (2014) Crystal structure of a human GABAA receptor. Nature doi: 10.1038/nature13293:1-8.
8. Li GD, Chiara DC, Sawyer GW, Husain SS, Olsen RW, et al. (2006) Identification of a GABAA receptor anesthetic binding site at subunit interfaces by photolabeling with an etomidate analog. J Neurosci 26: 11599-11605.
9. Chiara DC, Dostalova Z, Jayakar SS, Zhou X, Miller KW, et al. (2012) Mapping general anesthetic binding site(s) in human alpha1beta3 gamma-aminobutyric acid type A receptors with [(3)H]TDBzl-etomidate, a photo-reactive etomidate analogue. Biochemistry 51: 836-847.
10. Jayakar SS, Zhou X, Chiara DC, Dostalova Z, Savechenkov PY, et al. (2014) Multiple Propofol Binding Sites in a gamma-Aminobutyric Acid Type A Receptor (GABAAR) Identified Using a Photoreactive Propofol Analog. J Biol Chem 289: 456-468.
11. Li GD, Chiara DC, Cohen JB, Olsen RW (2010) Numerous classes of general anesthetics inhibit etomidate binding to gamma-aminobutyric acid type A (GABAA) receptors. J Biol Chem 285: 8615-8620.
12. Stewart DS, Hotta M, Li GD, Desai R, Chiara DC, et al. (2013) Cysteine Substitutions Define Etomidate Binding and Gating Linkages in the alpha-M1 Domain of gamma-Aminobutyric Acid Type A (GABAA) Receptors. J Biol Chem 288: 30373-30386.
13. Bali M, Akabas MH (2004) Defining the propofol binding site location on the GABAA receptor. Mol Pharmacol 65: 68-76.
14. Stewart DS, Hotta M, Desai R, Forman SA (2013) State-Dependent Etomidate Occupancy of Its Allosteric Agonist Sites Measured in a Cysteine-Substituted GABAA Receptor. Mol Pharmacol 83: 1200-1208.
15. Krasowski MD, Nishikawa K, Nikolaeva N, Lin A, Harrison NL (2001) Methionine 286 in transmembrane domain 3 of the GABAA receptor beta subunit controls a binding cavity for propofol and other alkylphenol general anesthetics. Neuropharmacology 41: 952-964.
16. Stewart DS, Desai R, Cheng Q, Liu A, Forman SA (2008) Tryptophan mutations at azi-etomidate photo-incorporation sites on alpha-1 or beta-2 subunits enhance GABAA receptor gating and reduce etomidate modulation Mol Pharmacol 74: 1687-1695.
17. Bali M, Jansen M, Akabas MH (2009) GABA-induced intersubunit conformational movement in the GABAA receptor alpha1M1-beta2M3 transmembrane subunit interface: Experimental basis for homology modeling of an intravenous anesthetic binding site. J Neurosci 29: 3083-3092.
18. Borghese CM, Hicks JA, Lapid DJ, Trudell JR, Harris RA (2014) GABA(A) receptor transmembrane amino acids are critical for alcohol action: disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative location of binding sites. J Neurochem 128: 363-375.
19. Lynagh T, Lynch JW (2012) Ivermectin binding sites in human and invertebrate Cys-loop receptors. Trends Pharmacol Sci 33: 432-441.
20. Hibbs RE, Gouaux E (2011) Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474: 54-60.
21. Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MD, et al. (1997) Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors. Nature 389: 385-389.
22. Belelli D, Lambert JJ, Peters JA, Wafford K, Whiting PJ (1997) The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid. Proc Natl Acad Sci U S A 94: 11031-11036.
23. Hill-Venning C, Belelli D, Peters JA, Lambert JJ (1997) Subunit-dependent interaction of the general anaesthetic etomidate with the gamma-aminobutyric acid type A receptor. Br J Pharmacol 120: 749-756.
24. Siegwart R, Jurd R, Rudolph U (2002) Molecular determinants for the action of general anesthetics at recombinant alpha(2)beta(3)gamma(2)gamma-aminobutyric acid(A) receptors. J Neurochem 80: 140-148.
25. Siegwart R, Krahenbuhl K, Lambert S, Rudolph U (2003) Mutational analysis of molecular requirements for the actions of general anaesthetics at the gamma-aminobutyric acidA receptor subtype, alpha1beta2gamma2. BMC Pharmacol 3: 13.
26. Jurd R, Arras M, Lambert S, Drexler B, Siegwart R, et al. (2003) General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA(A) receptor beta3 subunit. FASEB J 17: 250-252.
27. Desai R, Rüsch D, Forman SA (2009) Gamma-amino butyric acid type A receptor mutations at beta2N265 alter etomidate efficacy while preserving basal and agonist-dependent activity. Anesthesiology 111: 774-784.
28. Bertaccini EJ, Yoluk O, Lindahl ER, Trudell JR (2014) Assessment of homology templates and an anesthetic binding site within the gamma-aminobutyric acid receptor. Anesthesiology 119: 1087-1095.
29. Jansen M, Akabas MH (2006) State-dependent cross-linking of the M2 and M3 segments: Functional basis for the alignment of GABAA and acetylcholine receptor M3 segments. J Neurosci 26: 4492-4499.
30. Sauguet L, Howard RJ, Malherbe L, Lee US, Corringer PJ, et al. (2013) Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel. Nature Comm 4: 1697.
31. Yip GM, Chen ZW, Edge CJ, Smith EH, Dickinson R, et al. (2013) A propofol binding site on mammalian GABA receptors identified by photolabeling. Nature Chem Biol 9: 715-720.
32. McCracken ML, Borghese CM, Trudell JR, Harris RA (2010) A transmembrane amino acid in the GABAA receptor beta2 subunit critical for the actions of alcohols and anesthetics. J Pharmacol Exp Ther 335: 600-606.
33. Baumann SW, Baur R, Sigel E (2001) Subunit arrangement of gamma-aminobutyric acid type A receptors. J Biol Chem 276: 36275-36280.
34. Kaur KH, Baur R, Sigel E (2009) Unanticipated structural and functional properties of delta subunit containing GABAA receptors. J Biol Chem 284: 7889-7896.
35. Forman SA, Stewart D (2011) Mutations in the GABAA receptor that mimic the allosteric ligand etomidate. Meth Mol Biol 796: 317-333.
36. Li J, Abel R, Zhu K, Cao Y, Zhao S, et al. (2011) The VSGB 2.0 model: a next generation energy model for high resolution protein structure modeling. Proteins 79: 2794-2812.
37. Bali M, Akabas MH (2012) Gating-induced Conformational Rearrangement of the gamma-Aminobutyric Acid Type A Receptor beta-alpha Subunit Interface in the Membrane-spanning Domain. J Biol Chem 287: 27762-27770.
38. Guitchounts G, Stewart DS, Forman SA (2012) The Two Etomidate Sites in alpha1beta2gamma2 gamma-Aminobutyric Acid Type A Receptors Contribute Equally and Noncooperatively to Modulation of Channel Gating. Anesthesiology 116: 1235-1244.
39. Nishikawa K, Jenkins A, Paraskevakis I Harrison NL (2002) Volatile anesthetic actions on the GABAA receptors: Contrasting effects of alpha 1(S270) and beta 2(N265) point mutations. Neuropharmacology 42: 337-345.
40. Colquhoun D (1998) Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and of the effects of mutating receptors. Br J Pharmacol 125: 924-947.
41. Galzi JL, Edelstein SJ, Changeux J (1996) The multiple phenotypes of allosteric receptor mutants. Proc Natl Acad Sci U S A 93: 1853-1858.
42. Foadi N, Leuwer M, Demir R, Dengler R, Buchholz V, et al. (2010) Lack of positive allosteric modulation of mutated alpha(1)S267I glycine receptors by cannabinoids. Naunyn-Schmiedeberg's Arch Pharmacol 381: 477-482.
43. Borghese CM, Xiong W, Oh SI, Ho A, Mihic SJ, et al. (2012) Mutations M287L and Q266I in the glycine receptor alpha1 subunit change sensitivity to volatile anesthetics in oocytes and neurons, but not the minimal alveolar concentration in knockin mice. Anesthesiology 117: 765-771.
44. Lynagh T, Laube B (2014) Opposing effects of the anesthetic propofol at pentameric ligand-gated ion channels mediated by a common site. J Neurosci 34: 2155-2159.
45. Chiara DC, Jayakar SS, Zhou X, Zhang X, Savechenkov PY, et al. (2013) Specificity of intersubunit general anesthetic binding sites in the transmembrane domain of the human alpha1beta3gamma2 GABAA receptor. J Biol Chem 288: 19343-19357.
46. Savechenkov PY, Zhang X, Chiara DC, Stewart DS, Ge R, et al. (2012) Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic. J Med Chem 55: 6554-6565.
47. Nury H, Van Renterghem C, Weng Y, Tran A, Baaden M, et al. (2011) X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel. Nature 469: 428-431.
48. Husain SS, Ziebell MR, Ruesch D, Hong F, Arevalo E, et al. (2003) 2-(3-Methyl-3H-diaziren-3-yl)ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate: A derivative of the stereoselective general anesthetic etomidate for photolabeling ligand-gated ion channels. J Med Chem 46: 1257-1265.
49. Husain SS, Nirthanan S, Ruesch D, Solt K, Cheng Q, et al. (2006) Synthesis of trifluoromethylaryl diazirine and benzophenone derivatives of etomidate that are potent general anesthetics and effective photolabels for probing sites on ligand-gated ion channels. J Med Chem 49: 4818-4825.
50. Husain SS, Stewart D, Desai R, Hamouda AK, Li SG, et al. (2010) p-Trifluoromethyldiazirinyl-etomidate: a potent photoreactive general anesthetic derivative of etomidate that is selective for ligand-gated cationic ion channels. J Med Chem 53: 6432-6444.
51. Godefroi EF, Janssen PAJ, Van der Eycken CAM, Van Heertum AHMT, Niemegeers CJE (1965) DL-(1-arylalkyl)imidazole-5-carboxylate esters. A novel type of hypnotic agents. J Med Chem 56: 220-223.
52. Atucha E, Hammerschmidt F, Zolle I, Sieghart W, Berger ML (2009) Structure-activity relationship of etomidate derivatives at the GABA(A) receptor: Comparison with binding to 11beta-hydroxylase. Bioorg Med Chem Lett 19: 4284-4287.
53. Pejo E, Santer P, Jeffrey S, Gallin H, Husain SS, et al. (2014) Analogues of Etomidate: Modifications around Etomidate's Chiral Carbon and the Impact on In Vitro and In Vivo Pharmacology. Anesthesiology 121: 290-301.
54. Forman SA, Miller KW (2011) Anesthetic sites and allosteric mechanisms of action on Cys-loop ligand-gated ion channels. Can J Anaesth 58: 191-205.
55. Spurny R, Billen B, Howard RJ, Brams M, Debaveye S, et al. (2013) Multisite binding of a general anesthetic to the prokaryotic pentameric Erwinia chrysanthemi ligand-gated ion channel (ELIC). J Biol Chem 288: 8355-8364.