Different residues in the GABAA receptor benzodiazepine binding pocket mediate benzodiazepine efficacy and binding

Molecular Pharmacology

Volumn 80, Issue 1, 2011, Pages 14-22

  Morlock, Elaine V ^a   Czajkowski, Cynthia ^a  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; BENZODIAZEPINE; CYSTEINE; ESZOPICLONE; FLURAZEPAM; ZOLPIDEM; BENZODIAZEPINE DERIVATIVE;

AMINO ACID SUBSTITUTION; ANIMAL CELL; ARTICLE; BINDING AFFINITY; CHLORIDE CURRENT; CONCENTRATION RESPONSE; DRUG EFFICACY; DRUG RECEPTOR BINDING; NONHUMAN; OOCYTE; PRIORITY JOURNAL; SITE DIRECTED MUTAGENESIS; VOLTAGE CLAMP; XENOPUS LAEVIS; AMINO ACID SEQUENCE; ANIMAL; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; GENETICS; METABOLISM; MOLECULAR GENETICS; RAT; SEQUENCE HOMOLOGY;

AMINO ACID SEQUENCE; ANIMALS; BENZODIAZEPINES; BINDING SITES; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTAGENESIS, SITE-DIRECTED; RATS; RECEPTORS, GABA-A; SEQUENCE HOMOLOGY, AMINO ACID; XENOPUS LAEVIS;

EID: 79959304002     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.110.069542     Document Type: Article

References (44)

1. Amin J, Brooks-Kayal A, and Weiss DS (1997) Two tyrosine residues on the alpha subunit are crucial for benzodiazepine binding and allosteric modulation of gamma-aminobutyric acidA receptors. Mol Pharmacol 51:833-841. (Pubitemid 27224689)
2. Baumann SW, Baur R, and Sigel E (2002) Forced subunit assembly in alpha1beta2gamma2 GABAA receptors. Insight into the absolute arrangement. J Biol Chem 277:46020-46025.
3. Benson JA, Löw K, Keist R, Mohler H, and Rudolph U (1998) Pharmacology of recombinant gamma-aminobutyric acidA receptors rendered diazepam-insensitive by point-mutated alpha-subunits. FEBS Lett 431:400-404. (Pubitemid 28352398)
4. Berezhnoy D, Nyfeler Y, Gonthier A, Schwob H, Goeldner M, and Sigel E (2004) On the benzodiazepine binding pocket in GABAA receptors. J Biol Chem 279:3160-3168. (Pubitemid 38140548)
5. Boileau AJ, Baur R, Sharkey LM, Sigel E, and Czajkowski C (2002) The relative amount of cRNA coding for gamma2 subunits affects stimulation by benzodiazepines in GABA(A) receptors expressed in Xenopus oocytes. Neuropharmacology 43:695-700. (Pubitemid 35279577)
6. Boileau AJ and Czajkowski C (1999) Identification of transduction elements for benzodiazepine modulation of the GABA(A) receptor: three residues are required for allosteric coupling. J Neurosci 19:10213-10220. (Pubitemid 30228028)
7. Boileau AJ, Kucken AM, Evers AR, and Czajkowski C (1998) Molecular dissection of benzodiazepine binding and allosteric coupling using chimeric gamma-aminobutyric acidA receptor subunits. Mol Pharmacol 53:295-303. (Pubitemid 28099740)
8. Buhr A, Baur R, Malherbe P, and Sigel E (1996) Point mutations of the alpha 1 beta 2 gamma 2 gamma-aminobutyric acid(A) receptor affecting modulation of the channel by ligands of the benzodiazepine binding site. Mol Pharmacol 49:1080-1084.
9. A receptors influence affinities for benzodiazepine binding site ligands. Mol Pharmacol 52:676-682.
10. Buhr A and Sigel E (1997) A point mutation in the gamma2 subunit of gamma-aminobutyric acid type A receptors results in altered benzodiazepine binding site specificity. Proc Natl Acad Sci USA 94:8824-8829. (Pubitemid 27335124)
11. Campo-Soria C, Chang Y, and Weiss DS (2006) Mechanism of action of benzodiazepines on GABAA receptors. Br J Pharmacol 148:984-990. (Pubitemid 44543616)
12. Chang Y, Wang R, Barot S, and Weiss DS (1996) Stoichiometry of a recombinant GABAA receptor. J Neurosci 16:5415-5424.
13. Davies M, Bateson AN, and Dunn SM (1998) Structural requirements for ligand interactions at the benzodiazepine recognition site of the GABA(A) receptor. J Neurochem 70:2188-2194. (Pubitemid 28207845)
14. Davies M, Newell JG, Derry JM, Martin IL, and Dunn SM (2000) Characterization of the interaction of zopiclone with gamma-aminobutyric acid type A receptors. Mol Pharmacol 58:756-762.
15. Derry JM, Dunn SM, and Davies M (2004) Identification of a residue in the gamma-aminobutyric acid type A receptor alpha subunit that differentially affects diazepam-sensitive and -insensitive benzodiazepine site binding. J Neurochem 88:1431-1438. (Pubitemid 38366919)
16. Downing SS, Lee YT, Farb DH, and Gibbs TT (2005) Benzodiazepine modulation of partial agonist efficacy and spontaneously active GABA(A) receptors supports an allosteric model of modulation. Br J Pharmacol 145:894-906. (Pubitemid 41129011)
17. Farrar SJ, Whiting PJ, Bonnert TP, and McKernan RM (1999) Stoichiometry of a ligand-gated ion channel determined by fluorescence energy transfer. J Biol Chem 274:10100-10104.
18. Ghanouni P, Gryczynski Z, Steenhuis JJ, Lee TW, Farrens DL, Lakowicz JR, and Kobilka BK (2001) Functionally different agonists induce distinct conformations in the G protein coupling domain of the beta 2 adrenergic receptor. J Biol Chem 276:24433-24436.
19. Goldschen-Ohm MP, Wagner DA, Petrou S, and Jones MV (2010) An epilepsy-related region in the GABA(A) receptor mediates long-distance effects on GABA and benzodiazepine binding sites. Mol Pharmacol 77:35-45.
20. Hanson SM and Czajkowski C (2008) Structural mechanisms underlying benzodiazepine modulation of the GABA(A) receptor. J Neurosci 28:3490-3499. (Pubitemid 351469312)
21. Hanson SM, Morlock EV, Satyshur KA, and Czajkowski C (2008) Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem 51:7243-7252.
22. Kloda JH and Czajkowski C (2007) Agonist-, antagonist-, and benzodiazepine-induced structural changes in the alpha1 Met113-Leu132 region of the GABAA receptor. Mol Pharmacol 71:483-493. (Pubitemid 46147915)
23. Kucken AM, Wagner DA, Ward PR, Teissére JA, Boileau AJ, and Czajkowski C (2000) Identification of benzodiazepine binding site residues in the gamma2 subunit of the gamma-aminobutyric acidA receptor. Mol Pharmacol 57:932-939. (Pubitemid 30253376)
24. Lavoie AM and Twyman RE (1996) Direct evidence for diazepam modulation of GABAA receptor microscopic affinity. Neuropharmacology 35:1383-1392. (Pubitemid 27013874)
25. Mellor JR and Randall AD (1997) Frequency-dependent actions of benzodiazepines on GABAA receptors in cultured murine cerebellar granule cells. J Physiol 503:353-369. (Pubitemid 27423361)
26. 2 subunit determines benzodiazepine efficacy. J Biol Chem 269:32768-32773.
27. Möhler H, Fritschy JM, and Rudolph U (2002) A new benzodiazepine pharmacology. J Pharmacol Exp Ther 300:2-8. (Pubitemid 34028501)
28. Ortells MO and Lunt GG (1995) Evolutionary history of the ligand-gated ion-channel superfamily of receptors. Trends Neurosci 18:121-127.
29. Rogers CJ, Twyman RE, and Macdonald RL (1994) Benzodiazepine and beta-carboline regulation of single GABAA receptor channels of mouse spinal neurones in culture. J Physiol 475:69-82.
30. Rüsch D and Forman SA (2005) Classic benzodiazepines modulate the open-close equilibrium in alpha1beta2gamma2L gamma-aminobutyric acid type A receptors. Anesthesiology 102:783-792. (Pubitemid 40462858)
31. Sancar F and Czajkowski C (2011) Allosteric modulators induce distinct movements at the GABA-binding site interface of the GABA-A receptor. Neuropharmacology 60:520-528.
32. Schaerer MT, Buhr A, Baur R, and Sigel E (1998) Amino acid residue 200 on the alpha1 subunit of GABA(A) receptors affects the interaction with selected benzodiazepine binding site ligands. Eur J Pharmacol 354:283-287. (Pubitemid 28401462)
33. Sieghart W and Sperk G (2002) Subunit composition, distribution and function of GABA(A) receptor subtypes. Curr Top Med Chem 2:795-816.
34. Sigel E and Buhr A (1997) The benzodiazepine binding site of GABAA receptors. Trends Pharmacol Sci 18:425-429. (Pubitemid 27521060)
35. Swaminath G, Deupi X, Lee TW, Zhu W, Thian FS, Kobilka TS, and Kobilka B (2005) Probing the beta2 adrenoceptor binding site with catechol reveals differences in binding and activation by agonists and partial agonists. J Biol Chem 280:22165-22171. (Pubitemid 40827872)
36. Swaminath G, Xiang Y, Lee TW, Steenhuis J, Parnot C, and Kobilka BK (2004) Sequential binding of agonists to the beta2 adrenoceptor. Kinetic evidence for intermediate conformational states. J Biol Chem 279:686-691. (Pubitemid 38044873)
37. Tan KR, Baur R, Gonthier A, Goeldner M, and Sigel E (2007a) Two neighboring residues of loop A of the alpha1 subunit point towards the benzodiazepine binding site of GABAA receptors. FEBS Lett 581:4718-4722. (Pubitemid 47432773)
38. Tan KR, Gonthier A, Baur R, Ernst M, Goeldner M, and Sigel E (2007b) Proximity-accelerated chemical coupling reaction in the benzodiazepine-binding site of gamma-aminobutyric acid type A receptors: superposition of different allosteric modulators. J Biol Chem 282:26316-26325. (Pubitemid 47443788)
39. Thompson SA, Smith MZ, Wingrove PB, Whiting PJ, and Wafford KA (1999) Mutation at the putative GABA(A) ion-channel gate reveals changes in allosteric modulation. Br J Pharmacol 127:1349-1358. (Pubitemid 29358935)
40. Twyman RE, Rogers CJ, and Macdonald RL (1989) Differential regulation of gamma-aminobutyric acid receptor channels by diazepam and phenobarbital. Ann Neurol 25:213-220. (Pubitemid 19085510)
41. Venkatachalan SP, Bushman JD, Mercado JL, Sancar F, Christopherson KR, and Boileau AJ (2007) Optimized expression vector for ion channel studies in Xenopus oocytes and mammalian cells using alfalfa mosaic virus. Pflugers Arch 454:155-163. (Pubitemid 46355868)
42. Wieland HA and Lüddens H (1994) Four amino acid exchanges convert a diazepaminsensitive, inverse agonist-preferring GABAA receptor into a diazepampreferring GABAA receptor. J Med Chem 37:4576-4580.
43. A receptors is essential for benzodiazepine agonist binding. J Biol Chem 267:1426-1429.
44. A receptor that determine ligand binding and modulation at the benzodiazepine site. Mol Pharmacol 52:874-881.