ライフサイエンスコーパス: allosteric site

1 rs depending on what dNTP is bound in the A2 allosteric site.

2 bstrate ATP, indicating that they act via an allosteric site.

3 Ras.GDP cannot properly activate Sos at the allosteric site.

4 ugh interaction with a previously unrevealed allosteric site.

5 opriate model receptor for investigating the allosteric site.

6 ds designed to bind irreversibly to the CB1R allosteric site.

7 (176), a trigger between the active site and allosteric site.

8 ed by the binding of an effector to a distal allosteric site.

9 ected by different dNTP ligands bound in the allosteric site.

10 with two orthosteric binding modes and to an allosteric site.

11 ed that they most likely used an overlapping allosteric site.

12 refined to recognize lorazepam in a putative allosteric site.

13 ut not ppGpp-positively regulates SAS1 at an allosteric site.

14 AChR by loop II without penetration into the allosteric site.

15 compounds acting at a common, transmembrane allosteric site.

16 tly with the orthosteric site and part of an allosteric site.

17 he active site or occupation of a regulatory allosteric site.

18 active site of PBP2a within the core of the allosteric site.

19 t screening hit that binds in a nonconserved allosteric site.

20 crease in NADP-ME2 activity by binding to an allosteric site.

21 lecules activate relaxin receptor through an allosteric site.

22 ibition potency supporting recognition of an allosteric site.

23 site and suggests the presence of a second, allosteric site.

24 that the inhibitor unexpectedly binds to an allosteric site.

25 ition in switch II upon ligand binding at an allosteric site.

26 etects the binding of ligands to this unique allosteric site.

27 I1, a BRAF inhibitor that fully uncovers the allosteric site.

28 d results from binding of this vitamer at an allosteric site.

29 ligand that binds specifically to the mGluR5 allosteric site.

30 mOctR, and alpha2C-adrenergic receptor at an allosteric site.

31 eatures regulate access of AZ10606120 to the allosteric site.

32 , an HspQ binding site and an HspQ-modulated allosteric site.

33 e that these inhibitors bind to the proposed allosteric site.

34 red by an inability to precisely control the allosteric site.

35 e for high-throughput searches for candidate allosteric sites.

36 control of protein function by modulation of allosteric sites.

37 vation and the absence of broadly applicable allosteric sites.

38 state of the protein when they bind to their allosteric sites.

39 dulate nAChR function by binding to distinct allosteric sites.

40 involving binding to both the catalytic and allosteric sites.

41 hich successfully identifies orthosteric and allosteric sites.

42 r Cys-loop receptors, by binding to distinct allosteric sites.

43 c activity by dGTP binding at four identical allosteric sites.

44 effective inhibitors and help identify novel allosteric sites.

45 r energetic coupling with Phe binding in the allosteric sites.

46 odulation by ligands acting through numerous allosteric sites.

47 he highly conserved ACh-binding site, termed allosteric sites.

48 the adenine/guanine mononucleotides for the allosteric sites.

49 r ligand binding pockets and orthosteric and allosteric sites.

50 hosphorylase activity or the location of its allosteric sites.

51 nactive kinase conformations, or act through allosteric sites.

52 all molecules that are able to interact with allosteric sites.

53 ion of cooperativity between orthosteric and allosteric sites.

54 D1 is activated by binding of GTP or dGTP at allosteric site 1 and a dNTP of any type at allosteric s

55 allosteric site 1 and a dNTP of any type at allosteric site 2.

56 Moreover, ATP and dATP bind at an additional allosteric site 40 A away from loop 2 and thereby drive

57 ic EF1143 contains four additional secondary allosteric sites adjacent to the previously identified d

58 d potency derived from a 50-fold increase in allosteric site affinity as compared with BQCA, while re

59 This allosteric site allows for selective inhibition with res

60 rovides new insights into the mechanisms and allosteric sites [alpha(-)-interface containing] by whic

61 Surprisingly, mutations in the allosteric site also abolished the voltage-dependence of

62 cribed to stem from sole interaction with an allosteric site, although the evidence for such a mechan

63 unexpected presence of a previously unknown allosteric site and an unusual dodecameric structure for

64 sight into dNTP promiscuity at the secondary allosteric site and how enzymatic activity is modulated.

65 f a FRET-based sensor of conformation at the allosteric site and in pharmacological assays involving

66 es on the reciprocal interactions between an allosteric site and its coupled orthosteric site.

67 losteric transition, we vary the size of the allosteric site and its interactions to construct a seri

68 ropose that Plasmodium Kinesin-5 shares this allosteric site and likewise can be targeted to uncover

69 of structural information regarding the A1AR allosteric site and mechanisms governing cooperativity w

70 not exhibit sodium ion binding to the D2.50 allosteric site and samples a significantly larger confo

71 ctively inhibit mutant IDH1 by binding to an allosteric site and that inhibition is competitive with

72 3) pharmacological compounds targeting this allosteric site and utilizing this mode of inhibition.

73 of a protein provides valuable insights into allosteric sites and communication pathways.

74 rk corresponding to biologically significant allosteric sites and pathways.

75 at there are many as yet undiscovered hidden allosteric sites and suggests our methodology can identi

76 lin domain, conducted the cross-talk between allosteric sites and the mannoside-binding pocket.

77 tanding of the biological relevance of these allosteric sites and the way forward to design more-pote

78 and FTSite are useful tools for identifying allosteric sites and to aid in the design of such compou

79 efined orthosteric binding site and possible allosteric sites and to analyze the importance of the li

80 the experimental approaches designed to map allosteric sites and transitions.

81 concomitant association with orthosteric and allosteric sites) and that the compound displays biased

82 r binding, post-translational modifications, allosteric sites, and catalytic residues.

83 Affinities of isoflurane and propofol to the allosteric site are also calculated, and shown to be 3 m

84 hibition is cooperative, indicating that the allosteric sites are not independent despite being locat

85 nowledge of the target site, but most hidden allosteric sites are only discovered when a small molecu

86 The results identify the location of the allosteric site as the interface of the regulatory domai

87 that incorporates competition for active and allosteric sites, as well as functional sequestration of

88 us, the current study identifies novel c-Src allosteric sites associated with imatinib binding and ki

89 e D3R(Dopa) model are predicted to occupy an allosteric site at the extracellular extension of the po

90 op that hinders methoctramine binding to the allosteric site at this receptor subtype.

91 acting with both the orthosteric site and an allosteric site, at the M(1) mAChR.

92 Here, we review algorithms that predict allosteric sites based on sequence data and molecular dy

93 structures revealed 3 binds to an unexpected allosteric site between the C-terminal and the N-termina

94 om the orthosteric site up toward a putative allosteric site bordered by TM2, TM3, and TM7, thus cons

95 he modulator's high binding affinity for the allosteric site but not for generating allostery on the

96 ctive protein kinase inhibitors by targeting allosteric sites, but these sites often involve protein-

97 However, interaction with an allosteric site by an antagonist fragment of TBPB was de

98 lactam antibiotics, wherein occupancy at the allosteric site by one facilitates occupancy by a second

99 Kinetic analysis reveals co-occupancy of the allosteric sites by TIH and L-histidine.

100 vity via non-competitive antagonism from two allosteric sites, by channeling the inhibition towards t

101 by which glucose 6-phosphate binding at the allosteric site communicates with the PykA active site.

102 y result in a higher affinity of dTTP to the allosteric site conferring its inhibitory activity.

103 The sodium ion site is an allosteric site conserved among many G protein-coupled r

104 In addition, we discuss how targeting of allosteric sites could provide new opportunities to inhi

105 l structure shows that the compound binds an allosteric site created by the displacement of the regul

106 Upon binding a metal ion in the allosteric site, CueR switches into an activator conform

107 with PBP2a-each with the beta-lactam in the allosteric site-defined (with preceding PBP2a structures

108 antagonists bind to CCR4 at an intracellular allosteric site denoted site II.

109 Compounds targeting the allosteric site display a variety of functional activity

110 The basis for this discrimination is an allosteric site, distal from the active site, that when

111 Unexpectedly, these drugs all bind to an allosteric site distinct from the ATP-binding pocket in

112 two inhibitor molecules interact within the allosteric site, driving significant conformational chan

113 Based on increasing interest in allosteric-site drug discovery, we foresee many potentia

114 m in adult liver, harbors two noninteracting allosteric sites, each of which binds a different molecu

115 gest that tiotropium binds transiently to an allosteric site en route to the binding pocket of both r

116 ly inhibit the KRAS isoform by binding to an allosteric site encompassing the region around KRAS-spec

117 of the cytosolic region was found to have an allosteric site for acyl-CoA/CoA.

118 binding site, SERT possesses a low affinity allosteric site for antidepressants.

119 Here we identified this allosteric site for efavirenz on CYP46A1 by using a comb

120 The location of the allosteric site for phenylalanine has not been establish

121 noceptor (alpha(1B)-AR) to help identify the allosteric site for rho-conopeptide TIA, an inverse agon

122 he activators, identifying it as a versatile allosteric site for Sirt6 modulation.

123 We show that the H3 pocket is an allosteric site for the regulation of the rotation of th

124 ntrinsic flexibility of RT can provide novel allosteric sites for inhibition.

125 cleos(t)ide analogues as well as a number of allosteric sites for nonnucleos(t)ide inhibitors.

126 ol of protein allostery and design of unique allosteric sites for potential enzyme inhibitors with re

127 ibitors of RPTPs but a scarcity of validated allosteric sites for RPTPs.

128 ng configuration as S-trityl analogues at an allosteric site formed by loop L5 of Eg5.

129 Rather, we propose that a transient propofol allosteric site forms when the motor head binds to the m

130 s of decoupling the identification of hidden allosteric sites from the discovery of drugs that bind t

131 This allosteric site greatly enhances the 'druggability' of A

132 stinct from the orthosteric sites, so-called allosteric sites, has heralded novel approaches and mode

133 Several allosteric sites have been identified within the family

134 -domain shows that they bind to the I-domain allosteric site (IDAS), the binding site of other allost

135 Binding to the allosteric site impedes dissociation of antidepressants

136 Furthermore, the presence of a novel allosteric site in an intermediate state of c-src that c

137 ng mode involving residues within TM10 in an allosteric site in BGT1 that corresponds to the alloster

138 ransfer (CEST) interactions with the primary allosteric site in bla give rise to a unique saturation

139 of a cytohesin-3 construct encompassing the allosteric site in complex with the head group of phosph

140 st evidence, to our knowledge, for a cryptic allosteric site in CTX-M-9 beta-lactamase.

141 1,013 compounds for possible binding to the allosteric site in farnesyl diphosphate synthase (FPPS).

142 Here, we identified a potential allosteric site in GPX4 and successfully found eight GPX

143 We further identify the location of an allosteric site in the complex as residing at the periph

144 he active conformation, whereas targeting an allosteric site in the dimer interface selects an inacti

145 ings show a novel mode of agonism through an allosteric site in the extracellular domain of alpha7 nA

146 rlaps with the previously described "common" allosteric site in the extracellular vestibule of the M1

147 complex show that (S)-CPP binds to a unique allosteric site in the N-terminal domain, triggering hel

148 ligand binding to the prototypical MPEP/FPEB allosteric site in vitro.

149 rotein backbone is used to identify putative allosteric sites in a series of antibody fragments.

150 ion of these methods reveals multiple hidden allosteric sites in an important antibiotic target--TEM-

151 Drug-like molecules targeting allosteric sites in proteins are of great therapeutic in

152 es a simple method for identification of new allosteric sites in PTP, and given the basis of this met

153 However, it has been a challenge to identify allosteric sites in target proteins where insertion of r

154 is approach, we apply it to discover cryptic allosteric sites in two different beta-lactamase enzymes

155 some GPCRs possess more than one targetable allosteric site, in addition to a growing list of putati

156 this loop motion to effector binding at the allosteric site, in order to identify the signaling path

157 yme toward 2-AG, whereas 2-AG binding at the allosteric site increases COX-2's efficiency toward AA.

158 stent with Na(+) binding to an extracellular allosteric site, independent of the ion transport sites,

159 e example of this, we have introduced distal allosteric sites into molecular beacons, which are optic

160 f arsenic-bound p53 mutants reveal a cryptic allosteric site involving three arsenic-coordinating cys

161 et Mtb-fumarase by binding to a nonconserved allosteric site is a major advancement, providing furthe

162 The affinity of NMS at the allosteric site is in the micromolar range for all recep

163 y inhibit RNA synthesis, suggesting that the allosteric site is not always available during RNA synth

164 When this allosteric site is occupied, a multiresidue conformation

165 One allosteric site is surface-exposed and is located near t

166 ystal structures, a possible location of the allosteric site is within a cleft between the alpha- and

167 straightforward approach to identify hidden allosteric sites is demonstrated in protein tyrosine pho

168 Therefore, targeting allosteric sites is gaining increasing recognition as a

169 mimics of the acyl-D-Ala-D-Ala moiety at the allosteric site, lead to a conformational change, across

170 eptors suggest that TCN-201 binds to a novel allosteric site located at the dimer interface between t

171 Previously, a model was created for an allosteric site located between the flap and the core of

172 We extended previous observations that an allosteric site located in the vestibule of the receptor

173 These findings establish that three allosteric sites located at the PKAc N and C termini coo

174 involved variation at positions primarily at allosteric sites located outside of binding pockets, whe

175 these observations, we propose that cryptic allosteric sites may be even more ubiquitous than previo

176 ric sites, the force of anaesthetics through allosteric sites may not propagate to the neighbouring s

177 also influence the activity by binding to an allosteric site, most likely the pseudosymmetric site lo

178 ggable pocket that is the most intracellular allosteric site observed in class A G-protein-coupled re

179 ne the first view of a polyamine bound in an allosteric site of an N-acetyltransferase.

180 ompetitive interaction of AA and 2-AG at the allosteric site of COX-2 might result in differential re

181 a revealed that binding of AA or 2-AG at the allosteric site of COX-2 results in a decreased catalyti

182 ity in the dimer interface could serve as an allosteric site of hTS to regulate the conformational sw

183 ovel binding mode in a previously identified allosteric site of IDH1 (R132H).

184 the glutamatergic neurotransmission (glycine allosteric site of NMDA receptors or alpha-amino-3-hydro

185 ocument that this mimicry exists also at the allosteric site of PBP2a of methicillin-resistant Staphy

186 ability of the quinazolinones to bind to the allosteric site of penicillin-binding protein (PBP)2a, r

187 ovalent metal ions indirectly influences the allosteric site of Pfk-2 by increasing its affinity for

188 weakly binds to the catalytic but not to the allosteric site of Sos.

189 OS, bringing GDP-Ras to the proximity of the allosteric site of SOS.

190 drogens of human androgen receptor (AR), the allosteric site of the AR binding function 3 (BF3) was i

191 tion mutagenesis in a single position of the allosteric site of the dimer interface, and we show that

192 ts as an allosteric ligand that binds at the allosteric site of the enzyme's interfacial surface, shi

193 (11)C-ABP688, a PET ligand that binds to an allosteric site of the metabotropic glutamate 5 receptor

194 o affinity of (11)C-ABP688 for binding to an allosteric site of the metabotropic glutamate 5 receptor

195 ompounds showed type III interaction with an allosteric site of the proteins.

196 ility of structure-based screening targeting allosteric sites of GPCRs.

197 o provides an effective approach to identify allosteric sites of multimeric enzymes in general.

198 several EPAC1 mutants that target different allosteric sites of the cAMP-binding domain (CBD).

199 t form a network linking the orthosteric and allosteric sites of the M4 receptor, which provides new

200 al approach to discover a previously unknown allosteric site on 15-LOX.

201 complex shows that NSC13345 binds to a novel allosteric site on cathepsin K.

202 es, we find that Org 27569 binds to a unique allosteric site on CB1 and show that it can act alone (w

203 G may recognize more than one anion-binding, allosteric site on FXIa.

204 ligands and describes another example of an allosteric site on G-protein-coupled receptors that can

205 work has extensively characterized a common allosteric site on mGlu5, termed the MPEP (2-Methyl-6-(p

206 ydroxyb enzamide), interacts with a separate allosteric site on mGlu5.

207 the same GarA FHA-binding pocket targets an allosteric site on nonphosphorylated KGD, where a key el

208 iously described the identification of a new allosteric site on the catalytic alpha-subunit, along wi

209 ecific drug-protein interactions validate an allosteric site on the channel periphery and its relevan

210 artial inverse agonist at the benzodiazepine allosteric site on the gamma-aminobutyric acid (GABA)(A)

211 s, EGFR and HER2, is achieved by engaging an allosteric site on the HER3 kinase domain, but this site

212 However, LY2119620 also binds to an allosteric site on the human M2 subtype.

213 structure to LY2033298 and binds to the same allosteric site on the human M4 mAChRs.

214 proach to targeting a functionally conserved allosteric site on the protein kinase PDK1 called the PD

215 AChR), but it possesses low affinity for the allosteric site on the receptor.

216 ch is a small molecule that binds to a novel allosteric site on the surface of beta-catenin.

217 induced by ligand binding to orthosteric or allosteric sites on a G protein-coupled receptor (GPCR)

218 These data suggest the orthosteric and allosteric sites on CHRMs respond differently to divalen

219 To probe directly the allosteric sites on M2 and M4, we radiolabeled LY2119620

220 subtype specificity achievable by targeting allosteric sites on mGlu receptors.

221 took advantage of the many tools for probing allosteric sites on mGlu(5) to validate an operational m

222 hanced receptor gating by rapidly binding to allosteric sites on open channels, initiating a rate-lim

223 Computational methods to predict allosteric sites on proteins are needed to aid the disco

224 mal modes can enhance our ability to predict allosteric sites on proteins.

225 nslational modifications or metal binding to allosteric sites on the enzyme, which stabilize inactive

226 There are at least four distinct allosteric sites on the polymerase to which several smal

227 has spurred current research into targeting allosteric sites on these receptors.

228 At this allosteric site, ORG27569 promotes an intermediate confo

229 Assays showed that NIT acts on an allosteric site other than the dimerization interface.

230 Two other RNA molecules bind DNMT3A at an allosteric site outside the catalytic domain, causing no

231 Antagonist AZ3451 binds to a remote allosteric site outside the helical bundle.

232 gonist MK-0893, which is found to bind to an allosteric site outside the seven transmembrane (7TM) he

233 ion of these residues is consistent with two allosteric sites per dimer, with each site containing re

234 f rhodopsin-like GPCRs suggest that specific allosteric sites play a pivotal role in activating struc

235 s with mGlu5 modulators have relied on mGlu5 allosteric site positron emission tomography (PET) radio

236 et regions in LF did not, suggesting that an allosteric site preferentially recognizes alpha-helical

237 Competition of AM-8138 for the allosteric site prevented the inhibition of COX-2-depend

238 g (25 angstrom) of single-stranded DNA in an allosteric site primes the active site by conformational

239 Allosteric sites provide targets to fine-tune protein ac

240 by the effector, modeled by the size of the allosteric site, provides an order parameter for alloste

241 cy may result from binding of propofol to an allosteric site recently identified by X-ray crystallogr

242 Finding small molecules that target allosteric sites remains a grand challenge for ligand di

243 ic potential of these pockets--called hidden allosteric sites--remains unclear.

244 simulations wherein substrate binding to an allosteric site remote from the active site opens up cha

245 ee-dimensional NMR solution structure of the allosteric site revealed an alpha-helix with a loop conn

246 ary, a novel inhibitor scaffold targeting an allosteric site shared between flaviviral NS2B/NS3 prote

247 This model revealed that the active and allosteric sites show cooperativity.

248 Calcium acetate binding in the allosteric site stabilizes the conformation observed in

249 Occupancy of the allosteric site sterically hinders ligand unbinding from

250 th anesthetics have a lower affinity for the allosteric site than for the unoccupied pore.

251 were more significantly enriched at protein allosteric sites than tolerated mutations, suggesting a

252 Here, we describe the discovery of a SULT1A3 allosteric site that can be used to inhibit the enzyme.

253 in a protein involves effector binding at an allosteric site that changes the structure and/or dynami

254 However, 1 also bound an alternate/allosteric site that could alternatively account for the

255 GTP relieves autoinhibition by binding to an allosteric site that includes the autoinhibitory element

256 esent a cryptic drug-binding pocket near the allosteric site that may be amenable to targeting with s

257 (-) binding to a high-affinity non-transport allosteric site that prevents Na(+) from binding to one

258 thway connecting the active site to the main allosteric site that remains in the substrate-bound form

259 Instead, omecamtiv mecarbil binds to an allosteric site that stabilizes the lever arm in a prime

260 xperiments, the human Kinesin-5 has multiple allosteric sites that are "druggable." One site in parti

261 p38gamma contains allosteric sites that are conserved among eukaryotic kin

262 of BCR-ABL have led to the identification of allosteric sites that are distant from the ATP-binding p

263 erefore, have shifted to the exploitation of allosteric sites that can regulate phosphatase activity

264 t propofol is not binding at the ATP site or allosteric sites that modulate microtubule-activated ATP

265 hods were also able to find partially hidden allosteric sites that were not fully formed in X-ray str

266 r, DF2593A, guided by the hypothesis that an allosteric site, the "minor pocket," previously characte

267 This process is tightly regulated via two allosteric sites, the specificity site (s-site) and the

268 Here, the first structure of an NSAID allosteric site-the MEF-binding site of SULT1A1-is deter

269 anism by binding to a previously undescribed allosteric site: the interface of the two cAMP binding d

270 is class of inhibitors acts by binding to an allosteric site; the novel binding site is proposed in s

271 re capable of forming a complex with the SOS allosteric site, thus aberrantly promoting SOS autoactiv

272 n that couples effector ligand binding at an allosteric site to a structural and/or dynamic change at

273 ta2 loop, and beta4 loop and functions as an allosteric site to enhance the efficiency of activation

274 rotonin (5-HT) 5-HT(2C) receptor (5-HT(2C)R) allosteric site to potentiate endogenous 5-HT tone may p

275 ly important for signal propagation from the allosteric site to the active site.

276 ay for the signal transmission from the P450 allosteric site to the active site.

277 ent pathways of signal transduction from the allosteric site to the active site.

278 In particular, the transmission from the allosteric site to the signaling surface of the receiver

279 3A binds H3 tails and p53 or TDG at distinct allosteric sites to form DNMT3A-H3 tail-p53 or -TDG mult

280 strate the utility of purposefully targeting allosteric sites to obtain mutant-selective inhibitors.

281 samples across 33 cancer types into protein allosteric sites to prioritize the mutated allosteric pr

282 y nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional p

283 rtant insights into the structural bases for allosteric site-to-active site communication and for bet

284 Cryptic allosteric sites--transient pockets in a folded protein

285 A topographically distinct allosteric site was identified based on the newly solved

286 mGluR5 receptor binding specifically to an allosteric site was observed by using positron emission

287 To target this putative allosteric site, we generated and characterized fragment

288 connections between the active site and the allosteric site were indicated by equilibrium binding ex

289 The two allosteric sites were shown to regulate the binding of a

290 increase in affinity for the peptide in the allosteric site when KIX is prebound by a complementary

291 of the cube also provided a distinct second allosteric site, where the binding of tetraphenylborate

292 opentenyl diphosphate, IPP) site, not to the allosteric site, whereas zoledronate bound via Mg(2+) to

293 is model was validated by mutagenesis of the allosteric site, which led to constitutively active SARM

294 tions allows us to identify potential hidden allosteric sites, which we then test via thiol labeling

295 radiolabeled [11C]ABP688, which binds to an allosteric site with high specificity.

296 however, has been on modes of targeting GPCR allosteric sites with chemical probes due to the potenti

297 dies indicate that dGTP binding to the first allosteric site, with nanomolar affinity, is a prerequis

298 y of discovery programs focused on targeting allosteric sites, with allosteric ligands now available

299 83% and 88% of such experimentally confirmed allosteric sites within the three strongest sites found.

300 to be expected that binding of Na(+) to the allosteric site would be nearly saturated.