ライフサイエンスコーパス: allosteric modulation

1 icking, channel gating, agonist potency, and allosteric modulation.

2 changes at position E172C in the absence of allosteric modulation.

3 mmaMet-299) likely to be a site for positive allosteric modulation.

4 issociation kinetics, ligand specificity and allosteric modulation.

5 (GABA(A)) receptor during channel gating and allosteric modulation.

6 ch may render them particularly sensitive to allosteric modulation.

7 esidues critical for receptor activation and allosteric modulation.

8 ding, and also long alkyl amides are without allosteric modulation.

9 ral correlates of activation, antagonism and allosteric modulation.

10 o investigate the structural determinants of allosteric modulation.

11 petitive antagonists; both drugs act through allosteric modulation.

12 with different headgroups display a range of allosteric modulation.

13 to form an intracellular 'skirt' involved in allosteric modulation.

14 idence for a purely efficacy-driven positive allosteric modulation.

15 nderstanding of the structural basis of mGlu allosteric modulation.

16 he pyrrolidinyl ring is not required for CB1 allosteric modulation.

17 nerated significant interest in CB1 receptor allosteric modulation.

18 linker, consistent with its contribution to allosteric modulation.

19 value alpha < 1, thus indicating a negative allosteric modulation.

20 icity of drug action that can be provided by allosteric modulation across a GPCR homodimeric interfac

21 g allosteric agonism in addition to positive allosteric modulation (ago-PAMs).

22 ough negative (alpha6beta1delta) or positive allosteric modulation (alpha4beta2delta, alpha6beta2,3de

23 h dimer modeling provides insights about the allosteric modulation and activation mechanism of class

24 The concepts of allosteric modulation and biased agonism are revolutioni

25 foundation for mechanisms of ligand-gating, allosteric modulation and ion permeation.

26 We examined the effects on allosteric modulation and ligand binding of the mutation

27 e binding process suggests opportunities for allosteric modulation and provides a structural foundati

28 Further issues discussed include allosteric modulation and the role of water molecules in

29 n the context of ligand binding, activation, allosteric modulation, and biased signaling.

30 f effects, ranging from positive to negative allosteric modulation, and includes compounds that do no

31 ectivity; mechanisms for desensitization and allosteric modulation; and mechanisms for partial agonis

32 l determinants for positive and negative BZD allosteric modulation are different.

33 and quantifying ligand-biased signaling and allosteric modulation at CB1Rs, revealing ligand-biased

34 y, we quantified ligand-biased signaling and allosteric modulation at CB1Rs.

35 ssociation of [(3)H]S-1 from the S1 site via allosteric modulation at S2.

36 ing to unravel the mechanistic basis of GPCR allosteric modulation at the molecular level.

37 d to influence receptor conformation through allosteric modulation, biased signaling, and selectivity

38 d and tested for sensitivity to glycine, and allosteric modulation by alcohols.

39 ng periods of prolonged stimulation, whereas allosteric modulation by ATP may help to modulate intrac

40 The lack of additional, pathway-biased, allosteric modulation by BQCA was confirmed in genetical

41 Allosteric modulation by cis-(Z)-flupentixol involves a

42 played probe-dependent and pathway-dependent allosteric modulation by concentrations of zinc reported

43 0-one in the central nervous system, and its allosteric modulation by fluoxetine has been linked to t

44 d type A (GABA(A) )receptors are targets for allosteric modulation by general anesthetics.

45 s residues of the GABA(A) alpha-3 subunit in allosteric modulation by isoflurane.

46 amily" of ion channels, and are sensitive to allosteric modulation by n-alcohols such as ethanol and

47 Mutation at TM2(D79N) reduces allosteric modulation by Na(+) and receptor activation m

48 llustrates the possibility that the locus of allosteric modulation by PD 81,723 may be manifest via a

49 ith delta subunit also affected the negative allosteric modulation by pregnenolone sulfate.

50 and kinetically distinct from rapid positive allosteric modulation by PregS.

51 critical role in channel gating by GABA and allosteric modulation by propofol.

52 n a way which is subjected to structural and allosteric modulation by the weak zinc-binding C-termina

53 Thrombin undergoes allosteric modulation by thrombomodulin (TM) that result

54 ctivation by allosteric agonism, rather than allosteric modulation, could be responsible for the adve

55 Strikingly, these allosteric modulations disappear on agonist and antagoni

56 irectly inhibit the proteolysis of MMP-9 via allosteric modulation exclusively at the ligand specific

57 for these sites, combined with differential allosteric modulation, gives rise to a complex interplay

58 Over the past 20 years, our understanding of allosteric modulation has grown significantly, and numer

59 es a highly sensitive yardstick to probe the allosteric modulation in contrast to the traditionally u

60 c receptors and sheds light on mechanisms of allosteric modulation in nAChRs, especially the subtle d

61 pecific electrostatic interactions drive the allosteric modulation in the PDZ3 domain protein.

62 he absence of GABA and demonstrated positive allosteric modulation in the presence of GABA, whereas b

63 further substantiating a multisite model of allosteric modulation in this family of ion channels.

64 ssing native Y4R, demonstrating Y4R positive allosteric modulation in vitro.

65 XCR4 at the CXCL12 binding pocket suggesting allosteric modulation, in accordance with our electrophy

66 t alterations in either thermal stability or allosteric modulation increase starch synthesis.

67 and stereochemistry can affect the degree of allosteric modulation, indicating an unforeseen selectiv

68 Allosteric modulation is a mechanism for modifying pharm

69 must exist in the drug-bound enzyme and that allosteric modulation is effected via the alteration of

70 e role of intracellular domains in mediating allosteric modulation is largely unknown.

71 tes that the initial phase of rapid positive allosteric modulation is not a first step in NMDAR upreg

72 This allosteric modulation may be direct, involving binding t

73 eceptor, which provides new insight into how allosteric modulation may be transmitted between the two

74 Allosteric modulation may yield a change in the activity

75 s strongly support the hypothesis that mGluR allosteric modulation occurs via stabilization of differ

76 ion by sevoflurane results from the positive allosteric modulation of activation gating.

77 Allosteric modulation of adenosine A1 receptors (A1ARs)

78 ional model of allosterism that accounts for allosteric modulation of affinity, efficacy, and alloste

79 In this study, allosteric modulation of agonist binding and function at

80 emotional responses by reducing the positive allosteric modulation of Allo at GABA(A) receptors in co

81 trast to direct agonist activation, positive allosteric modulation of alpha7 nAChRs would deliver the

82 r with either agonist activation or positive allosteric modulation of alpha7 nAChRs.

83 in gating and represents a hub for powerful allosteric modulation of AMPA receptor function that can

84 vity, and five produced significant positive allosteric modulation of atropine-reversible, direct-ago

85 llular loop 2 of the B1R results in positive allosteric modulation of B1R signaling, and disruption o

86 [Sar(1),Ile(4),Ile(8)]-AngII exerts lateral allosteric modulation of B2 receptor signaling by bindin

87 conclude that rifamycins do not function by allosteric modulation of binding of Mg(2+) to the RNAP a

88 et al. proposed that rifamycins function by allosteric modulation of binding of Mg(2+) to the RNAP a

89 ansmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine recept

90 ith a domain interface model for binding and allosteric modulation of Ca2+ channel activity by DHPs.

91 ional studies demonstrated that MCV1 acts by allosteric modulation of calcineurin.

92 Allosteric modulation of catalysis kinetics is prevalent

93 Positive allosteric modulation of CB1-receptor signaling shows pr

94 al requirements of indole-2-carboxamides for allosteric modulation of CB1: a critical chain length at

95 no inherent agonism but maintained positive allosteric modulation of CCL3 binding.

96 Together our findings suggest that the allosteric modulation of channel gating involves distinc

97 rather with the loss of stargazin-associated allosteric modulation of channel gating.

98 tic specificity and offers new insights into allosteric modulation of channel gating.

99 ng site may represent a common mechanism for allosteric modulation of class A GPCRs.

100 sms that contribute to positive and negative allosteric modulation of classical ligand binding, inclu

101 ant new tool compound for the exploration of allosteric modulation of COX enzymes and their role in e

102 For the G-protein-uncoupled receptor, allosteric modulation of CRF binding was correlated with

103 chemokine CXCL14 synergizes with CXCL12 via allosteric modulation of CXCR4.

104 sms of fast inhibitory neurotransmission and allosteric modulation of Cys-loop receptors.

105 e our understanding of a multisite model for allosteric modulation of Cys-loop receptors.

106 de-binding lectins, exhibit subunit-specific allosteric modulation of desensitization of recombinant

107 23 and 26) is consistent with noncompetitive allosteric modulation of dopamine signaling in the extra

108 bout whether this equivalence extends to the allosteric modulation of DREADDs by small molecules.

109 ic approach to evaluate the role of positive allosteric modulation of each of the four diazepam-sensi

110 ole of PH domains in regulating catalysis by allosteric modulation of enzyme structure.

111 us have suggested that this effect involves allosteric modulation of factor IXa.

112 Allosteric modulation of G-protein-coupled receptors rep

113 f fluoxetine or fluvoxamine via its positive allosteric modulation of GABA type A receptors.

114 naplon produces an anxiolytic action through allosteric modulation of GABA(A) receptors.

115 ons in SI mice appears to be elicited by the allosteric modulation of GABA(A)-Rs overexpressing alpha

116 Moreover, negative allosteric modulation of GABAA receptors impaired social

117 ort the involvement of the M4 segment in the allosteric modulation of GABArho1 by DPA.

118 ma2 and gamma8, we could entirely remove all allosteric modulation of GluA2, without affecting format

119 Allosteric modulation of GPCRs has initiated a new era o

120 ss of positive modulators and establish that allosteric modulation of hERG channel function through l

121 s of hmGluR3, completely eliminated LY487379 allosteric modulation of hmGluR2.

122 In this study, the allosteric modulation of human A(3) adenosine receptors

123 3's regulatory effects may stem in part from allosteric modulation of IF2-GAC interactions.

124 ion of a ubiquitin-dependent pathway through allosteric modulation of its E3 activity by small compou

125 ing the direction of information flow during allosteric modulation of its nucleotide-dependent intrin

126 suggest that sulfhydration of SUR2B induces allosteric modulation of K(ATP) currents in colonic infl

127 lecules act on synaptic transmission via the allosteric modulation of ligand-gated chloride channels,

128 neurotransmitter systems, drugs that provide allosteric modulation of ligand-gated ion channels or G-

129 s provide preliminary evidence that positive allosteric modulation of M1 is sufficient to elicit chol

130 This review focuses on positive allosteric modulation of metabotropic glutamate 2 recept

131 Positive allosteric modulation of metabotropic glutamate receptor

132 Acute positive allosteric modulation of mGlu5 or inhibition of endocann

133 the mGlu5/eCB signaling complex, by positive allosteric modulation of mGlu5 or inhibition of endocann

134 These results support positive allosteric modulation of mGlu5, particularly with VU0409

135 tance to extinction was reversed by positive allosteric modulation of mGluR5 during extinction traini

136 These data indicate that positive allosteric modulation of mGluR5 receptors facilitates th

137 Conversely, positive allosteric modulation of mGluR5 results in the exacerbat

138 utral cooperativity, preventing the positive allosteric modulation of mGluRs by DFB as well as the ne

139 is study provides structural evidence on the allosteric modulation of MgNTP(2-) on the NS3 helicase a

140 the mechanisms of orthosteric activation and allosteric modulation of muscarinic receptors.

141 t insights into the activation mechanism and allosteric modulation of muscarinic receptors.

142 ivation through the agonist binding site, an allosteric modulation of nAChR has also been described f

143 We are interested in the allosteric modulation of neuronal nicotinic acetylcholin

144 We are interested in the positive allosteric modulation of neuronal nicotinic acetylcholin

145 tructural requirements for the formation and allosteric modulation of NMDA receptor pores, we have re

146 extracellular Ca(2+) Reciprocally, positive allosteric modulation of P2X4 (ivermectin) augmented ATP

147 ication and maintain segment balance through allosteric modulation of polymerase activity.

148 nhibitory neurotransmission through positive allosteric modulation of postsynaptic GABAA receptors, i

149 Instead, we suggest an allosteric modulation of prestin by Cl- and other anions

150 hich we have perturbed, likely contribute to allosteric modulation of prestin via interactions among

151 These results suggest that the allosteric modulation of protein function by isoflurane,

152 ese interactions may provide a mechanism for allosteric modulation of receptor function.

153 eptors and vice versa, suggesting reciprocal allosteric modulation of receptors in the heterodimer.

154 data of RT in various states, details of the allosteric modulation of RT dynamics by NNRTIs are lacki

155 provide insights into how substrate-coupled allosteric modulation of structure and dynamics facilita

156 including a conserved drug-binding site for allosteric modulation of substrate proteolysis.

157 A mechanism for interdomain allosteric modulation of substrate-binding is proposed.

158 annel complex in a binary fashion; one is an allosteric modulation of the alpha1 subunit function and

159 f 9-aminoacridine compounds that demonstrate allosteric modulation of the alpha1A- and alpha1B-adrene

160 esents a novel class of molecules capable of allosteric modulation of the alpha7 nAChRs.

161 ntity of the subunit mediating the direct or allosteric modulation of the antidepressant effect on GA

162 viously identified site involved in positive allosteric modulation of the bacterial homolog ELIC.

163 We found that allosteric modulation of the CNO-bound DREADD receptor i

164 ently to divalent cations and the effects of allosteric modulation of the cortical CHRM1 is reduced i

165 Positive allosteric modulation of the GABA(A) receptor (GABA(A)R)

166 GABA(A) receptor-mediated ionic currents via allosteric modulation of the GABA(A) receptor.

167 fect of selection for ethanol sensitivity on allosteric modulation of the GABA-A receptor.

168 s to increase Abeta42 production may reflect allosteric modulation of the gamma-secretase complex by

169 n determining the functional consequences of allosteric modulation of the Gly-R by alcohols.

170 re synthesized and tested for their positive allosteric modulation of the HCA(2) receptor (GPR109A).

171 ion channel protein and postphosphorylation allosteric modulation of the I(Ks) channel by Yotiao.

172 Allosteric modulation of the Kv11.1 channel efficiently

173 Allosteric modulation of the ligand-binding domain by ho

174 difficult to confer the high sensitivity for allosteric modulation of the M2 subtype onto the weakly

175 In addition to allosteric modulation of the maximum functional efficacy

176 50% binding efficiency, suggesting there is allosteric modulation of the melanocortin-4 receptor.

177 Positive allosteric modulation of the mu-opioid receptor (MOPr),

178 isingly, Pepcan-12 exhibited potent negative allosteric modulation of the orthosteric agonist-induced

179 Allosteric modulation of the receptor has recently emerg

180 In complementary kinetic studies assessing allosteric modulation of the receptor, unlabeled THRX-16

181 Intriguingly, this allosteric modulation of the T3 channel is propagated th

182 However, allosteric modulation of their scaffolding abilities and

183 the molecular basis for agonist binding and allosteric modulation of these proteins is poorly unders

184 led TNF receptor (TNFR) function by inducing allosteric modulation of tryptophan-107 (W107) in the re

185 Ligand-biased signaling from, and allosteric modulation of, CB1Rs offer pharmacological ap

186 s to study the general mechanism of positive allosteric modulations of T1R taste receptors.

187 Thus, allosteric modulations of the cloned K(ATP) channel by A

188 , there is limited evidence of the impact of allosteric modulation on receptor regulatory mechanisms

189 o identify level and type (positive/negative allosteric modulation or full antagonism) of mGluR5 modu

190 dentified a novel chemotype for the positive allosteric modulation (PAM) of the muscarinic acetylchol

191 ace of cells despite receptor activation and allosteric modulation properties that mirror a wild-type

192 incorporate concepts of allosteric agonism, allosteric modulation, signaling bias, constitutive acti

193 t on orthosteric agonist responses but block allosteric modulation (silent allosteric modulators (SAM

194 RGS proteins by regulation of expression or allosteric modulation to permit either increases or decr

195 -tubocurarine and may be subject to negative allosteric modulation to varying degrees by different pu

196 og DU124183 had the most favorable degree of allosteric modulation versus receptor antagonism.

197 Thus, astrocytes are required for positive allosteric modulation via the alpha3 subunit benzodiazep

198 sults will be discussed in terms of indirect allosteric modulations via amino acid substitutions and/

199 ar agonist probe dependence in the nature of allosteric modulation was apparent.

200 The observed allosteric modulation was consistent in all the function

201 f caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by

202 esults demonstrate functional selectivity of allosteric modulations within the D1R-D3R heteromer, whi