ライフサイエンスコーパス: orthosteric

1 tion of their ability to inhibit or modulate orthosteric [(3)H]NMS binding revealed that para-LRB-AC4

2 tagonize) the receptor, and the third is the orthosteric activation (agonist) site.

3 ides crucial insights into the mechanisms of orthosteric activation and allosteric modulation of musc

4 rthosteric agonists, Tyr-93 can conduct both orthosteric activation and desensitization among the sub

5 hese mutations have no significant effect on orthosteric activation of 5-HT3ARs by 5-HT.

6 identify Tyr-93 as an essential element for orthosteric activation, because Y93C mutants are insensi

7 , and mutagenesis results suggested that the orthosteric agonist 5'-N-ethylcarboxamidoadenosine binds

8 he maximum response evoked by the endogenous orthosteric agonist 5-HT, respectively).

9 nous allosteric modulator of MOPr and alters orthosteric agonist affinity and efficacy.

10 anges are coupled between the extracellular, orthosteric agonist binding domain and the transmembrane

11 These positive allosteric modulators of orthosteric agonist binding nonetheless antagonized the

12 flytrap domain, a region generally known for orthosteric agonist binding.

13 568, the allosteric agonist neomycin, or the orthosteric agonist Ca(2+) (0.5 or 5 mm), suggesting tha

14 o the transmission of cooperativity with the orthosteric agonist carbachol.

15 e positively modulate the binding of the CB1 orthosteric agonist CP55,940 while exhibiting an antagon

16 positive allosteric modulator of binding of orthosteric agonist CP55,940.

17 sidues near the TM4-ECL2 juncture influenced orthosteric agonist efficacy.

18 nts showed that cinnabarinic acid acts as an orthosteric agonist interacting with residues of the glu

19 the M2 receptor simultaneously bound to the orthosteric agonist iperoxo and the positive allosteric

20 ffects on the modulation of responses to the orthosteric agonist l-quisqualate and the allosteric mod

21 intracellular Ca(2+) responses evoked by the orthosteric agonist l-quisqualate.

22 Residues involved in cooperativity with the orthosteric agonist NECA were different in PD81723 and V

23 lating the activity of the receptor when the orthosteric agonist occupies the receptor, thus maintain

24 that cinnabarinic acid is a novel endogenous orthosteric agonist of mGlu4 receptors endowed with neur

25 receptor 4 (mGlu4 receptor), either with an orthosteric agonist or a positive allosteric modulator (

26 Ms), and 5) compounds that have no effect on orthosteric agonist responses but block allosteric modul

27 duce signaling and also selectively traffics orthosteric agonist signaling via the ERK phosphorylatio

28 tion that were significantly up-regulated by orthosteric agonist stimulation.

29 M4 muscarinic acetylcholine receptor (mAChR) orthosteric agonist xanomeline (1) and the putative M1 m

30 ydroxylpropyl]cyclohe xan-1-ol (CP55,940, an orthosteric agonist) while at the same time decreasing i

31 positive cooperativity between BQCA and the orthosteric agonist, carbachol, across pathways.

32 his work expands the characterization of the orthosteric agonist, iperoxo, at the M(4) receptor, and

33 allosterically modulate the activity of the orthosteric agonist, R-PIA.

34 potent negative allosteric modulation of the orthosteric agonist-induced cAMP accumulation, [(35)S]GT

35 cellular-transmembrane interface accompanies orthosteric agonist-mediated gating.

36 enhance the affinity and/or efficacy of the orthosteric agonist.

37 or, this could be markedly increased by both orthosteric agonists and antagonists [15-, 9-, and 19-fo

38 of mGluR1alpha is adjacent to the site where orthosteric agonists and antagonists bind on the extrace

39 eviously reported to affect activities of M1 orthosteric agonists and antagonists were studied.

40 interact either directly or indirectly with orthosteric agonists and antagonists.

41 describe the first potent and selective FFA2 orthosteric agonists and demonstrate key aspects of liga

42 To date, most studies have been done with orthosteric agonists and/or antagonists at specific site

43 llosteric enhancers slow the dissociation of orthosteric agonists but not antagonists.

44 ion, because Y93C mutants are insensitive to orthosteric agonists but respond to GAT107.

45 d in vivo pharmacological actions of the CB1 orthosteric agonists CP55,940 and N-arachidonoylethanola

46 esis studies indicate that the compounds are orthosteric agonists despite the absence of a carboxylat

47 tivity binding of [(3)H]LY2119620 with mAChR orthosteric agonists detects significant changes in Bmax

48 -1-ol) and Delta(9)-tetrahydrocannabinol are orthosteric agonists for the receptor, bind the conventi

49 exhibiting high positive cooperativity with orthosteric agonists in a manner that correlated with ef

50 in penetrant, increased the potency of these orthosteric agonists in mouse behavioral assays indicati

51 Orthosteric agonists induce transitions between these co

52 increase the affinity and/or efficacy of the orthosteric agonists leu-enkephalin, SNC80 and TAN67, as

53 metabotropic glutamate receptors (mGluRs) or orthosteric agonists of mGluR2/3.

54 g evidence that activation by allosteric and orthosteric agonists results in different alpha7 nAChRs

55 responsive manner, whereas M1 allosteric and orthosteric agonists showed weak affinity (>30 muM).

56 acetylcholine receptor (nAChR) activation by orthosteric agonists with intrinsic allosteric agonist a

57 ional calcium mobilization assays to compare orthosteric agonists, acetylcholine and xanomeline, M1 a

58 toxin, a positive allosteric modulator, and orthosteric agonists, at 3.8 to 4.1 angstrom resolution.

59 the restraints placed on the requirement for orthosteric agonists, Tyr-93 can conduct both orthosteri

60 activate wild-type alpha7 in the absence of orthosteric agonists.

61 e adenosine A1 receptor amplify signaling by orthosteric agonists.

62 d was positively cooperative with muscarinic orthosteric agonists.

63 AMs) enhance the affinity and/or efficacy of orthosteric agonists.

64 ffects observed with nonselective muscarinic orthosteric agonists.

65 Undesirable side effects associated with orthosteric agonists/antagonists of cannabinoid 1 recept

66 Although PAMs must work in concert with "orthosteric" agonists, compounds such as GAT107 ((3aR,4S

67 d differential potentiation depending on the orthosteric-allosteric pairing, with the largest coopera

68 ed to the discovery of a new class of hybrid orthosteric/allosteric (bitopic) molecules.

69 Here we use the model of bitopic orthosteric/allosteric (i.e. dualsteric) agonists for mu

70 ive purely allosteric and the active bitopic orthosteric/allosteric binding pose.

71 hore via spacers of varying lengths, exhibit orthosteric/allosteric binding properties at muscarinic

72 lecular modeling studies focused on putative orthosteric/allosteric bitopic poses for AC-42 and para-

73 To reconcile this dual orthosteric/allosteric pharmacological behavior, we prop

74 Our data show that both orthosteric and allosteric activation of alpha7 nAChR re

75 h noncompetitively inhibited the activity of orthosteric and allosteric agonists at mGluR7.

76 Both orthosteric and allosteric antagonists of the group II m

77 ts into P2Y1R should enable discovery of new orthosteric and allosteric antithrombotic drugs with red

78 ata and evidence for the binding kinetics of orthosteric and allosteric AR ligands.

79 its a multivalent bimodal orientation in the orthosteric and allosteric binding pockets of mAChR and

80 eptor structures, reveals differences in the orthosteric and allosteric binding sites that contribute

81 on of M1 muscarinic receptors occurs through orthosteric and allosteric binding sites.

82 redictable from the properties of individual orthosteric and allosteric building blocks.

83 tations, as well as functional regulation by orthosteric and allosteric effectors.

84 This was dependent on both the orthosteric and allosteric ligand as no two allosteric-o

85 )-imido]triphosphate, suggests that both the orthosteric and allosteric ligands can alter the populat

86 nalysis of P2X4R kinetics and elucidates the orthosteric and allosteric mechanisms regulating its cha

87 ble high-throughput screens to identify both orthosteric and allosteric PLC inhibitors.

88 hat span and simultaneously bind to both the orthosteric and allosteric receptor sites.

89 of residues that form a network linking the orthosteric and allosteric sites of the M4 receptor, whi

90 These data suggest the orthosteric and allosteric sites on CHRMs respond differ

91 gagement (i.e., concomitant association with orthosteric and allosteric sites) and that the compound

92 ys a critical role in ligand binding to both orthosteric and allosteric sites.

93 te the transmission of cooperativity between orthosteric and allosteric sites.

94 g two pharmacophores to simultaneously adopt orthosteric and allosteric topography within a G protein

95 rom the extracellular environment as well as orthosteric and bitopic ligands with very different phys

96 Most ligands in the D3R(APO) model span both orthosteric and extended pockets and behave as antagonis

97 Here we performed virtual screening for orthosteric and putative allosteric ligands of the human

98 hed the inhibitory effect of the mGluR1alpha orthosteric antagonist (S)-alpha-methyl-4-carboxyphenylg

99 ration binding studies at the M2R, using the orthosteric antagonist atropine to determine unspecific

100 harmacological profile, decreased binding of orthosteric antagonist N-methylscopolamine to human M1-

101 clearly distinguished from the action of the orthosteric antagonist NMS.

102 Point mutations ruled out an orthosteric antagonist site.

103 n the discovery of a series of M5-preferring orthosteric antagonists based on the scaffold of 1,2,5,6

104 The orthosteric antagonists quinuclidinyl benzilate (QNB) an

105 o date were obtained with receptors bound to orthosteric antagonists, and only a few structures bound

106 he side effects associated with CB1 receptor orthosteric antagonists, negative allosteric modulators

107 other D2R "privileged structures" generated orthosteric antagonists.

108 cal trials have been conducted using several orthosteric antagonists.

109 terminal truncation leading to production of orthosteric antagonists.

110 Orthosteric beta-adrenergic receptor antagonists, known

111 te that the molecules bind deeply inside the orthosteric binding cavity.

112 rved NMR confirms 1 binds PPARgamma with two orthosteric binding modes and to an allosteric site.

113 firm that LY2119620 does not compete for the orthosteric binding pocket at any of the five muscarinic

114 utation of amino acid residues that form the orthosteric binding pocket caused a loss of carbachol re

115 nomeric and the dimeric compound bind to the orthosteric binding site (apparent Kd: 0.87 and 0.31 nM,

116 subtle differences in the highly homologous orthosteric binding site (OBS) differentially affect D2R

117 tween the D3R and D2R, especially within the orthosteric binding site (OBS) that binds dopamine, has

118 The existence of a high affinity primary orthosteric binding site (S1) and a low affinity seconda

119 Perspective is to identify the well-defined orthosteric binding site and possible allosteric sites a

120 olves simultaneous interaction with both the orthosteric binding site and the allosteric binding site

121 are a similar binding pocket adjacent to the orthosteric binding site at the opposite face of Trp101.

122 ne analogs bind at the monoamine transporter orthosteric binding site by adopting one of two mutually

123 Mutations within the orthosteric binding site caused similar reductions in af

124 Here, we investigate the pharmacology of the orthosteric binding site in GluD2 by examining the activ

125 tivated GLIC protein, exhibiting an uncommon orthosteric binding site in terms of sequence and local

126 oop receptors, involving an expansion of the orthosteric binding site in the extracellular domain tha

127 2), a compound supposed to interact with the orthosteric binding site of dopamine receptors, was actu

128 antagonists that exploit differences in the orthosteric binding site of GluN1 and GluN3 subunits, we

129 directionality of 5-substitutions inside the orthosteric binding site of the A(3) AR.

130 ed in brain tissues, did not compete for the orthosteric binding site of the CB(1) receptor (vs.

131 ex with TK40 and show that TK40 binds to the orthosteric binding site of the GluN1 subunit with a bin

132 r antagonism by ligands interacting with the orthosteric binding site of the receptor to incorporate

133 Whereas endogenous agonists acting at the orthosteric binding site stabilize the active receptor c

134 onal changes in the extracellular region and orthosteric binding site than observed in the active sta

135 zation-induced conformational changes in the orthosteric binding site underlie the voltage-dependence

136 formational coupling between the ECS and the orthosteric binding site, showing that drugs targeting t

137 R-selective compounds binds to the conserved orthosteric binding site, whereas the extended aryl amid

138 ically prevents dissociation of NMS from the orthosteric binding site.

139 nterface on the complementary surface of the orthosteric binding site.

140 in the vicinity of the 4-PHP scaffold in the orthosteric binding site.

141 activated by extracellular ATP through three orthosteric binding sites and allosterically regulated b

142 0 CH(2) groups) to simultaneously occupy two orthosteric binding sites in H(2)R dimers are nearly ina

143 ules are potentially able to interact at two orthosteric binding sites of a heterodimer simultaneousl

144 tor binding site partially overlaps with the orthosteric binding sites of class A GPCRs but is more r

145 of bitopic engagement of the allosteric and orthosteric binding sites of the receptor.

146 ng point mutations within the allosteric and orthosteric binding sites, as well as brain slice electr

147 r prevent the synergy between allosteric and orthosteric binding sites, so that these mutants can als

148 ned by independent actions on the respective orthosteric binding sites.

149 GPCR ligands due to the high conservation of orthosteric binding sites.

150 ir gating through a mechanism independent of orthosteric binding.

151 hically distinct from the endogenous ligand (orthosteric) binding site, allowing for co-occupation of

152 hically distinct from the endogenous ligand (orthosteric) binding site, which allows for co-occupatio

153 sidue seems to be located within or near the orthosteric-binding pocket and is not part of the allost

154 ructure of CCR2 in a ternary complex with an orthosteric (BMS-681) and allosteric (CCR2-RA-[R]) antag

155 of bipharmacophoric ligands composed of the orthosteric building blocks iperoxo and 1 linked to allo

156 ellular site, and atropine or scopolamine as orthosteric building blocks, both connected by a hexamet

157 nabinoid deactivation (JZL184, URB597) or an orthosteric cannabinoid agonist (WIN55,212-2).

158 rs of endocannabinoid deactivation and/or an orthosteric cannabinoid agonist.

159 lactic inactivation of CD11b/CD18, using the orthosteric CD11b/CD18 inhibitor mAb107, improves microv

160 Although displaying a common orthosteric component, the fluorescent compounds inherit

161 patially distinct sites: nucleotide MRS2500 (orthosteric, contacting the helical bundle) and urea BPT

162 we show progressive disruption of individual orthosteric contacts in the ligand binding sites, allowi

163 lation mediated via beta-arrestin unlike the orthosteric CP55,940 that does so in a G protein-depende

164 sp52(2.50) as an allosteric link between the orthosteric drug binding site and the intracellular sign

165 ein-coupled receptors respond to traditional orthosteric drugs are an exciting and rapidly expanding

166 prospect with many potential advantages over orthosteric drugs.

167 eceptor cavity that can bind allosteric (non-orthosteric) drugs.

168 ds were confirmed to be potent and selective orthosteric FFA2 agonists.

169 In the present study, the orthosteric GABAA receptor (GABAAR) ligand 4,5,6,7-tetra

170 The orthosteric GABAB receptor agonist baclofen has been sho

171 al view of an allosteric binding mode for an orthosteric GPCR ligand and provide additional opportuni

172 We find that orthosteric "head" groups with small 7-substituents were

173 ionalize oligonucleotides with biotin and an orthosteric inhibitor of the eukaryotic initiation facto

174 ones, also known as oncohistones, are potent orthosteric inhibitors of specific Su(var)3-9, Enhancer-

175 yses revealed that GIV3727 likely acts as an orthosteric, insurmountable antagonist of hTAS2R31.

176 having a significant role in contributing to orthosteric ligand affinity and signaling for various G

177 omparison of the effects of the modulator on orthosteric ligand affinity relative to signaling throug

178 ECL2-TM3 disulfide bond selectively affected orthosteric ligand affinity, whereas a cluster of five r

179 ct to ligand displacement but did not change orthosteric ligand affinity.

180 ence that was based upon the efficacy of the orthosteric ligand and can be explained using the Monod-

181 Both dissociation and binding of an orthosteric ligand are observed in a single all-atom GPC

182 standing of the role of the receptor core in orthosteric ligand binding and biological activity.

183 study highlights a key role for ECL2 in A1AR orthosteric ligand binding and receptor activation.

184 ational space that includes breathing of the orthosteric ligand binding site and shear motion of the

185 n of B2 receptor signaling by binding to the orthosteric ligand binding site of the AT1 receptor and

186 ffects of sodium ions and amiloride, whereas orthosteric ligand binding was decreased.

187 nd in this sodium ion site and can influence orthosteric ligand binding.

188 suggesting additional allosteric effects on orthosteric ligand efficacy.

189 the addition of a second mutation at a known orthosteric ligand interaction site, H6.55Q.

190 trate that the fusion of a fluorophore to an orthosteric ligand is not neutral, as it may confer, unl

191 perativity and negative allosteric effect on orthosteric ligand maximal signaling response.

192 569 and PSNCBAM-1 appeared to influence only orthosteric ligand maximum occupancy rather than affinit

193 c and allosteric ligand as no two allosteric-orthosteric ligand pairs could induce the same signaling

194 2 to explore the role of this domain on A1AR orthosteric ligand pharmacology.

195 When the orthosteric ligand pocket located in the transmembrane (

196 The sensitivity of an orthosteric ligand to BMS-986122 was strongly correlated

197 egative allosteric effects, depending on the orthosteric ligand used as a probe of receptor activity.

198 electivity problem by combining (linking) an orthosteric ligand with an allosteric modulator, theoret

199 ease involves potentiation of the endogenous orthosteric ligand, acetylcholine, at the M1 muscarinic

200 stin-biased signaling from occupation of the orthosteric ligand-binding pocket.

201 Also, the orthosteric ligand-binding site becomes the initiator re

202 d structural conservation extending from the orthosteric ligand-binding site in the transmembrane cor

203 ule, approximately 15 A from the classical, 'orthosteric' ligand-binding site.

204 a a different binding site than the natural (orthosteric) ligand site and hence form a conceptually d

205 ompared with drugs targeting the endogenous (orthosteric) ligand-binding site that include the abilit

206 voked signaling but also the actions of both orthosteric ligands and allosteric modulators on mGluR1a

207 timation of affinity and efficacy values for orthosteric ligands are not appropriate for allosteric m

208 estibule that overlaps with a region used by orthosteric ligands as they transit into the canonical A

209 can be differentially stabilized not only by orthosteric ligands but also by allosteric ligands actin

210 Cell-permeable orthosteric ligands can assist folding of G protein-coup

211 However, developing M1 mAChR-selective orthosteric ligands has proven challenging.

212 ng pathways and in combination with multiple orthosteric ligands in systems such as the GLP-1R where

213 the coupling between PAMs and the binding of orthosteric ligands requires tryptophan 55 (Trp-55), whi

214 renergic receptor (beta2AR) upon exposure to orthosteric ligands with different efficacies, in the ab

215 Interaction of orthosteric ligands with extracellular domain was descri

216 pond differently in the presence of discrete orthosteric ligands, a behavior termed "probe dependence

217 Under equilibrium binding conditions, orthosteric ligands, AC-42, and the allosteric modulator

218 hese compounds do not compete for binding of orthosteric ligands, but indeed the R isomer increased t

219 7569, offer enormous potential as drugs over orthosteric ligands, but their mechanistic, structural,

220 compound has no effect on the binding of the orthosteric ligands, implying its allosteric mode of act

221 Unlike orthosteric ligands, which tonically activate or inhibit

222 binding competition with serotonin or other orthosteric ligands.

223 122, with a chemically diverse range of MOPr orthosteric ligands.

224 efficacy for both selective and prototypical orthosteric ligands.

225 able to induce bias in signaling mediated by orthosteric ligands.

226 olecule drugs with substantial benefits over orthosteric ligands.

227 ostatic repulsion between the allosteric and orthosteric ligands.

228 and mechanisms governing cooperativity with orthosteric ligands.

229 h drugs that act as allosteric modulators of orthosteric ligands.

230 Identification of orthosteric mGlu(2/3) receptor agonists capable of discr

231 ructural information about the nature of the orthosteric muscarinic binding site (the conventional ac

232 ntrations up to 1 mM did not compete for the orthosteric nAChR binding site labeled by [(3)H]epibatid

233 nd 5b binds to pH sensor of ASIC1a acting as orthosteric noncompetitive antagonist.

234 olerance and dependence issues compared with orthosteric opioid receptor agonists.

235 retase presents several hot spots for either orthosteric or allosteric inhibition of catalytic activi

236 ologic activity induced by ligand binding to orthosteric or allosteric sites on a G protein-coupled r

237 e or negative, depending upon the allosteric-orthosteric pair, and they arose from interactions withi

238 In contrast, orthosteric PAR1 antagonists such as vorapaxar inhibit a

239 ng modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close

240 l)benzenesulfonamide (1, T2384) revealed two orthosteric pocket binding modes attributed to a concent

241 The orthosteric pocket is formed by residues conserved in th

242 , Tyr5.47, and Tyr6.48 and another above the orthosteric pocket lined by Asp2.65 and Tyr7.32.

243 inhibits chemokine binding by occupying the orthosteric pocket of the receptor in a previously unsee

244 he high degree of structural homology in the orthosteric pocket, particularly for GPCRs within a sing

245 mation and binds to the receptor deep in the orthosteric pocket, stabilizing a network of extracellul

246 nt binding poses are revealed for ARC in the orthosteric pocket.

247 ues in the intracellular, extracellular, and orthosteric pockets is significantly weakened upon sodiu

248 ed nucleophilic residues near and within the orthosteric pockets of M(1) and M(2) muscarinic receptor

249 diated allosteric effect is dependent on the orthosteric probe that is used.

250 es was assessed by their ability to displace orthosteric radioligand [(3)H]4-(2-((7-amino-2-(furan-2-

251 ptor binding with a series of allosteric and orthosteric radioligands at structurally related CCK1R a

252 ed changes in the dissociation rates for the orthosteric radioligands, [N-methyl-(3)H]scopolamine met

253 t of affinity for allosteric modulators with orthosteric radioligands, which has so far been the most

254 Delta(9)-tetrahydrocannabinol and other CB1 orthosteric receptor agonists remain limited because of

255 ligands that bind allosterically outside the orthosteric receptor binding pocket.

256 ML290 did not directly compete with orthosteric relaxin binding and did not affect binding k

257 Mutation of the orthosteric residue Phe168 to alanine abrogated the func

258 of IBMX based on their interactions with the orthosteric residues of PDE8.

259 y distinct from that of previously described orthosteric RORgammat ligands.

260 further show that selected mutations in the orthosteric site abolish the fluorescence signal and con

261 ls the entry and efflux of agonists from the orthosteric site and agonist binding elicits a conformat

262 a bitopic ligand, interacting with both the orthosteric site and an allosteric site, at the M(1) mAC

263 echanism, interacting concomitantly with the orthosteric site and part of an allosteric site.

264 ligands that compete with each other at the orthosteric site and two ligands that compete with each

265 the two novel bitter blockers share the same orthosteric site as the agonist quinine.

266 tes because their activity requires that the orthosteric site be occupied by an agonist, thereby conf

267 dulate the 5-HT(3) receptor, not through the orthosteric site but by binding to allosteric sites.

268 stent with a competitive binding mode at the orthosteric site by TBPB and fragment derivatives.

269 the expected change in affinity of the CHRM1 orthosteric site for acetylcholine in human cortex.

270 lthough it is well established that the A1AR orthosteric site is located within the receptor's transm

271 to agonists or antagonists that bind to the orthosteric site of the receptor.

272 r the development of compounds that bind the orthosteric site of this receptor.

273 ing to the binding of LY2033298, whereas the orthosteric site residues, Tyr104(3.33) and Tyr403(6.51)

274 The contacts found for the orthosteric site satisfy all the requirements deduced fr

275 Visual opsins bind 11-cis retinal at an orthosteric site to form rhodopsins but increasing evide

276 a binding pose predicted to extend from the orthosteric site up toward a putative allosteric site bo

277 tween subunits in a topologically conserved "orthosteric site" whose amino acid composition defines t

278 e extracellular entrance, in addition to the orthosteric site, allowed us to obtain 5-HT7R antagonist

279 lu4, mGlu6, and mGlu8 receptors with its own orthosteric site, and (2) that chloride is not an agonis

280 sts, such as acetylcholine (ACh), bind to an orthosteric site, located at subunit interfaces in the e

281 ng of a neurotransmitter to an extracellular orthosteric site, located at the interface of two adjace

282 nd-binding site blocking the entrance to the orthosteric site.

283 inding pocket is located below the classical orthosteric site.

284 s between an allosteric site and its coupled orthosteric site.

285 site but not for generating allostery on the orthosteric site.

286 nct from AC-42 and TBPB overlapping with the orthosteric site.

287 118925 and anthraquinones likely bind to the orthosteric site.

288 prior to entry into the canonical TM bundle orthosteric site.

289 ands as they transit into the canonical A1AR orthosteric site.

290 the alpha-Ctx-binding sites overlap with the orthosteric sites at the beta/alpha subunit interface.

291 tion of compounds that directly acted on the orthosteric sites for endogenous ligands.

292 ngest functional group interaction in enzyme orthosteric sites offers a rational starting point for F

293 Orthosteric sites on proteins are formed typically from

294 receptors topographically distinct from the orthosteric sites, so-called allosteric sites, has heral

295 in contrast to the global impact of GABA via orthosteric sites, the force of anaesthetics through all

296 ll activation paradigm via allosteric versus orthosteric sites, we used highly homologous, but homo-o

297 ective and less toxic than those that target orthosteric sites.

298 However, targeting PAR1 with an orthosteric-tethered ligand binding-site antagonist resu

299 receptors can simultaneously occupy both the orthosteric transmitter binding site and the allosteric

300 t a difference in spatial orientation of the orthosteric tropane moiety translates into a divergent M