ライフサイエンスコーパス: allosteric

1 s of CK2alpha has recently been described as allosteric, acting at a previously unidentified binding

2 ently developed computational model for CB1R allosteric activation and positive allosteric modulation

3 co docking of 2,3,5,6TMP-TQS in the putative allosteric activation binding site suggested a specific

4 sed mechanisms for substrate recognition and allosteric activation by low pH and chloride.

5 residues from TrpB that are crucial for its allosteric activation by TrpA.

6 And 2) in the allosteric activation mechanism, G protein allostericall

7 n of the (-) enantiomer with alpha7T106, and allosteric activation of alpha7T106 mutants was not inhi

8 helps to generalize a novel paradigm for the allosteric activation of kinase function and may open op

9 ues critical for complex formation abrogated allosteric activation of LegK7 both in vitro and within

10 Heterotropic allosteric activation of protein function, in which bind

11 Here we demonstrate the direct allosteric activation of proto-oncogene kinase Src by GP

12 inhibits protein synthesis by preventing the allosteric activation of the essential GTPase Initiation

13 At least two interdependent allosteric activation pathways originate at the FVIIa:sT

14 supporting the existence of two TF-mediated allosteric activation pathways.

15 teric modulator" and an antagonist of alpha7 allosteric activation, shares the same scaffold with thr

16 g a substrate of LegK7, also functions as an allosteric activator of its kinase activity.

17 a define the bPBP pedestal domain as the key allosteric activator of RodA both in vitro and in vivo,

18 t to rationally design the effector to be an allosteric activator or inhibitor is likely to be benefi

19 n of the fructose 1,6-bisphosphate (FBP), an allosteric activator, binding site, impacting the intera

20 s provide a mechanistic basis for developing allosteric activators of PDE6 with therapeutic implicati

21 al AMPK activators that generate AMP, unlike allosteric activators, downregulated pMLC but only when

22 d receptor binding sites important for these allosteric activities.

23 The SAR findings and the enhanced allosteric activity in this class of allosteric modulato

24 ensitizing agent, whereas KK150 is devoid of allosteric activity.

25 and may lay new foundation in the design of allosteric agents.

26 Furthermore, WT mice treated with P2X4 allosteric agonist ivermectin had exacerbated renal IR i

27 91 (6r) and GAT593 (6s), exhibited augmented allosteric-agonist and PAM activities in neuronal cultur

28 channel level, activation by orthosteric and allosteric agonists appeared as openings in quick succes

29 re widely employed to characterize important allosteric and enzyme modulation effects.

30 Kinetic analysis revealed that allosteric and orthosteric activation mechanisms can be

31 The allosteric and torpedo models have been used for 30 yr t

32 e that could be blocked with systemic mGluR5 allosteric antagonism via MTEP.

33 nderstand the mode of action of the numerous allosteric antagonists of this important drug target.

34 nteracting partner over another, introducing allosteric 'bias' into the signaling system.

35 tor, which revealed a previously undescribed allosteric binding pocket.

36 nts in transmembrane domains 1 and 2 and the allosteric binding site between transmembrane domains 2

37 egulatory domain (Delta1-147), suggesting an allosteric binding site for recifin A on the regulatory

38 activated by ACh when PAMs were bound to the allosteric binding site in the transmembrane domain.

39 as PET tracers for the in vivo imaging of an allosteric binding site of the M4 receptor.

40 y, whereas preliminary data had indicated an allosteric binding site.

41 interaction and supporting the model of the allosteric binding site.

42 Thus we identify key elements of allosteric binding sites, and extend drug design possibi

43 noticed, in silico docking analysis supports allosteric binding to glutamate-gated chloride channels

44 Indeed, allosteric but not catalytic AURKA inhibitors sensitize

45 POLD1 formed during G1, and demonstrate that allosteric but not catalytic inhibitors prevent the chro

46 tic depletion of AURKA, or its inhibition by allosteric but not catalytic inhibitors, blocks the G1-S

47 ites on the beta-tryptase tetramer, inducing allosteric changes at the small interface.

48 Importantly, we also observe long-range allosteric changes in flanking helices consistent with w

49 ructural specificity, as manifested by large allosteric changes that activate the nucleosome remodeli

50 ubtype to any of its PA28 activator triggers allosteric changes that are specific to this 20S/PA28 pa

51 he need for monoubiquitination, we reveal an allosteric communication between the ubiquitination site

52 In this system, an intriguing allosteric communication has been suggested to control i

53 s in the GAFa and GAFb domains in forming an allosteric communication network.

54 r-activity of GDH through alteration of this allosteric communication network.

55 ed method, Ohm, to identify and characterize allosteric communication networks within proteins.

56 the second chromodomain, mediates long-range allosteric communication of cpSRP43 with its activating

57 regulations, including the investigation of allosteric communication pathways, protein-DNA/RNA inter

58 Catalytic Asp-239 controls hMGL allosteric communications and may be considered as an es

59 ations at different parts of MMP1 occurs via allosteric communications that can take place via intera

60 These findings shed light on allosteric conformational changes in PCSK9 required for

61 E: Ca(2+) binding to the mini-sensor induces allosteric conformational changes in the Ca(2+) transloc

62 that fast fluctuations are essential for the allosteric control of PTP1B activity.

63 exadentate ligands occurs with high positive allosteric cooperativity (alpha > 40), and the ligand is

64 The link between allosteric cooperativity and template-directed synthesis

65 We propose that allosteric coupling among the microswitches controls the

66 lving mutations that perturb a bidirectional allosteric coupling between ligand binding and coregulat

67 substrate binding, and show that a specific allosteric coupling between substrate binding and proton

68 is of HCN channels has suggested a direct or allosteric coupling between the voltage- and cNMP-depend

69 The allosteric coupling constant in K-type allosteric system

70 Here we test whether transmembrane allosteric coupling controls the potassium binding affin

71 Such allosteric coupling leads to cooperative binding of prot

72 unctions as an integrator node to coordinate allosteric coupling of the two ligand-binding sites.

73 Computational approaches for analysis of allosteric coupling provide inexpensive opportunities to

74 e provided by ELOB/C transmitting long-range allosteric crosstalk from the substrate through CUL5 to

75 A small molecule MIF inhibitor and an allosteric CXCR4 inhibitor counteract this function, rev

76 The insights may be used to develop allosteric, DDR1-specific, kinase inhibitors.

77 of the amphipathic alphaN-helix of GRK5 and allosteric disruption of kinase-RH domain interaction fo

78 However, often they are allosteric drivers.

79 predictivity of in silico methodologies for allosteric drug discovery and boost the development of c

80 suited for and may be involved in functional allosteric dynamics upon receptor binding.

81 at are responsible for this inversion of the allosteric effect, all 6 evolutionary TrpA and TrpB inte

82 tential binding site), leading to a negative allosteric effect.

83 tions of the target protein with substrates, allosteric effectors, or other proteins; or can trigger

84 opportunities to tune potency and agonism of allosteric effectors.

85 ns within the binding pocket, causing unique allosteric effects in the enzyme.

86 rectly interacts with substrates and induces allosteric effects in the protease domain of FVIIa.

87 In addition, acetylation attenuated the allosteric effects of ATP on NAT1.

88 -calmodulin to the C-terminus has long-range allosteric effects on the extracellular segments of the

89 Collectively, DDC-01-163 is a promising allosteric EGFR degrader with selective activity against

90 Here, we develop an allosteric EGFR degrader, DDC-01-163, which can selectiv

91 network of conformational transitions, with allosteric elements in each protomer orchestrating host

92 The protein-tyrosine phosphatase SHP2 is an allosteric enzyme critical for cellular events downstrea

93 is released and is followed by accelerative allosteric feedback autoactivation.

94 s of modulation of [(3)H]muscimol binding by allosteric GABAergic modulators such as barbiturates and

95 rs' second binding event, which serves as an allosteric "gatekeeper" defining the extent to which the

96 work provides mechanistic insights into the allosteric gating and regulation of CN-gated and nucleot

97 key interactions that may be responsible for allosteric gating in these channels.

98 results pave the way for the development of allosteric HDAC inhibitors and regulators to improve the

99 gy profile also captured the crucial role of allosteric IN inhibitors in promoting multimerization an

100 cular indicator displacement assays (IIDAs), allosteric indicator displacement assay (AIDAs), mechani

101 ch TDeltaS completely compensates DeltaH, no allosteric influence of effector binding on substrate af

102 ncluded in changes previously identified for allosteric inhibition by Phe.

103 therefore creates the geometry that permits allosteric inhibition of PRC2 by methylated H3K36 in tra

104 Allosteric inhibition of RORgammat is conceptually new,

105 cepsilonRI and CD23 is blocked by reciprocal allosteric inhibition, suggesting that the 2 receptors e

106 Tuning sensitivity to an allosteric inhibitor distinguishes IMPDH from other meta

107 We now show that the allosteric inhibitor JG98, that targets the cytosolic Hs

108 We determine that Akt allosteric inhibitor MK2206 drives distinct PH domain st

109 Trametinib is an extremely potent allosteric inhibitor of mitogen-activated protein kinase

110 t when cells are treated with rapamycin, the allosteric inhibitor of mTORC1.

111 reclinical models, we show that RMC-4550, an allosteric inhibitor of SHP2, induces antitumor immunity

112 SHP2 allosteric inhibitors can attenuate LLPS of SHP2 mutants

113 While a number of allosteric inhibitors have been reported for hepatitis C

114 we characterized the binding of several SHP2 allosteric inhibitors in intact cells.

115 nd 7-positions to afford 26 and 29 as potent allosteric inhibitors of HIV-1 integrase that exhibited

116 e is emerging interest in the development of allosteric inhibitors of RPTPs but a scarcity of validat

117 itiation whose inhibition through a class of allosteric inhibitors opens avenues for cancer therapy.

118 tion of the ABL2 kinase using small molecule allosteric inhibitors, but not ATP-competitive inhibitor

119 litate rational design of high-affinity SERT allosteric inhibitors.

120 cluding types I, I(1)/(2), and II as well as allosteric inhibitors.

121 nopeptide with a noncompetitive, potentially allosteric inhibitory mechanism at the nAChRs.

122 /off switch for function and shows extensive allosteric interactions involving both intra- and interr

123 Allosteric kinase inhibitors, such as cGMP analogs, offe

124 Subsequently, TPX2-mediated allosteric kinase regulation gradually evolved.

125 paths forward for the design of therapeutic allosteric kinase regulators.

126 in the LBD on coactivator, orthosteric, and allosteric ligand binding.

127 oupled self-activation state and a potential allosteric ligand-bound state.

128 sons identify essential elements of both the allosteric ligands and receptor binding sites important

129 extracellular protons act as orthosteric and allosteric ligands for multiple receptors and channels.

130 Cannabinoid 1 receptor (CB1R) allosteric ligands hold a far-reaching therapeutic promi

131 Structurally diverse orthosteric and allosteric ligands, including newly designed and synthes

132 el insights into the mechanisms of action of allosteric ligands, which are of increasing interest as

133 xample of an emerging class of proteins with allosteric-like behavior that originates from intrinsic

134 g process is highly cooperative and strongly allosteric, likely driven by a wave of interdependent co

135 and computational studies shed light on the allosteric linkage between two anion binding sites that

136 binding regions, (ii) alpha-interface at the allosteric lobe.

137 binding of SARM1's own substrate NAD+ in an allosteric location, away from the catalytic sites.

138 zolopyrimidines, a class of highly selective allosteric MALT1 inhibitors.

139 out cholesterol; this identified a potential allosteric mechanism by which cholesterol binding regula

140 clic nucleotides (cAMP and/or cGMP), but the allosteric mechanism by which this occurs is incompletel

141 Together, these data suggest an allosteric mechanism for activation involving a conforma

142 ane binding site for diazepam and suggest an allosteric mechanism for anaesthetic reversal by flumaze

143 We propose a revised allosteric mechanism for how CUL-E3 ligases function.

144 We propose that the allosteric mechanism of nickel-activated DNA binding by

145 mal growth factor receptor (EGFR) through an allosteric mechanism provides a potential therapeutic st

146 s is constrained by GFRalpha1, likely via an allosteric mechanism that can be overcome by increasing

147 e Ig3 domain promotes MALT1 activation by an allosteric mechanism that is essential for its biologica

148 y showed that CS employs a novel competitive-allosteric mechanism to selectively recruit its substrat

149 In the cooperative and allosteric mechanism, O(2) migrates to the catalytic hem

150 and appears to affect the channel gate by an allosteric mechanism.

151 t cause of nonadditivity, but the underlying allosteric mechanisms often remain elusive.

152 his direct-coupling mechanism contrasts with allosteric mechanisms proposed for hyperpolarization-act

153 uced Fzd/LRP6 heterodimerization, versus the allosteric mechanisms seen in structurally analogous cla

154 CTC1 at two separate docking sites, allowing allosteric mediation of CST decamer assembly.

155 a useful starting point for the discovery of allosteric MGL inhibitors.

156 assay may be used for the identification of allosteric modifiers of olfactory-driven behaviors capab

157 terol with CB1, suggestive of its endogenous allosteric modulating role.

158 Our findings suggest that positive allosteric modulation of AMPA receptors restores synapti

159 re mGlu(5) NAM binding kinetics and negative allosteric modulation of mGlu(5) receptor internalizatio

160 Allosteric modulation of NR activity constitutes a promi

161 molecular mechanism underlying the positive allosteric modulation of the MOP receptor by the Mg(2+)

162 ar determinants responsible for its positive allosteric modulation of the receptor, are unknown.

163 application of concepts such as signal bias, allosteric modulation, dual agonism, polymorphic recepto

164 by binding to active sites or exosites or by allosteric modulation.

165 eptor (GABA(A)R) contributes to neurosteroid allosteric modulation.

166 for CB1R allosteric activation and positive allosteric modulation.

167 a7 nicotinic acetylcholine receptor positive allosteric modulator (PAM) 3a,4,5,9b-Tetrahydro-4-(1-nap

168 n inhibitory neurons using an NMDAR positive allosteric modulator (PAM) elevates spiking activity of

169 S directly binds IDO1 and acts as a positive allosteric modulator (PAM) of the IDO1 enzyme in vitro a

170 Application of an mGluR2-positive allosteric modulator (PAM) reduced glutamate neurotransm

171 hronic administration of the mGluR4 positive allosteric modulator (PAM) VU0155041 (2.5 and 5 mg/kg) r

172 AGN-241751, an NMDAR positive allosteric modulator (PAM), is currently being tested as

173 eceptor to form a ternary complex, where the allosteric modulator affects the binding affinity and op

174 An allosteric modulator and an orthosteric agonist bind sim

175 his active state is stabilized by a positive allosteric modulator binding at the transmembrane dimeri

176 the antenna region, NADH acts as a positive allosteric modulator by enhancing both the affinity of t

177 Lastly, we show the positive allosteric modulator diazepam enhanced GABA-A currents o

178 and experimental evidence that GAT1508 is an allosteric modulator of channel-phosphatidylinositol 4,5

179 related to the loss of alcohol as a positive allosteric modulator of GABA(A) receptors, a decrease in

180 of action is that it is a selective positive allosteric modulator of glutamate-gated chloride channel

181 r concentrations, ivermectin also acts as an allosteric modulator of ion channels found in host centr

182 In addition, we found that an allosteric modulator of many class A GPCRs, Na(+), syner

183 6TMP-TQS), previously published as a "silent allosteric modulator" and an antagonist of alpha7 allost

184 e ability of a novel CB(1) receptor (CB(1)R) allosteric modulator, ABM300, to ameliorate these dysreg

185 a7 nicotinic acetylcholine receptor-negative allosteric modulator, BNC210, to 24 individuals (3 male

186 345, a novel dopamine D(1) receptor positive allosteric modulator, is being evaluated for the treatme

187 ation of an alpha5-GABA(A) receptor negative allosteric modulator, L-655,708, reproduces the sustaine

188 odimer is bound to an agonist and a positive allosteric modulator.

189 LIC bound either to a positive or a negative allosteric modulator.

190 LUF7244 as a negative allosteric modulator/activator in combination with dofet

191 ation of dofetilide plus LUF7244, a K(v)11.1 allosteric modulator/activator, to rescue K(v)11.1 traff

192 Negative allosteric modulators (NAMs) have shown promising result

193 n preclinical studies, many mGlu(5) negative allosteric modulators (NAMs) that have reached clinical

194 dulators (PAMs) and alpha5-GABA(A)R negative allosteric modulators (NAMs), which were originally deve

195 emplified by alpha2/alpha3-GABA(A)R positive allosteric modulators (PAMs) and alpha5-GABA(A)R negativ

196 on our recently described 5-HT(2C)R-positive allosteric modulators (PAMs) based on the 4-alkylpiperid

197 rinic acetylcholine receptor 4 (M4) positive allosteric modulators (PAMs) for the treatment of sympto

198 inic acetylcholine receptor (mAChR) positive allosteric modulators (PAMs) have been reported to enhan

199 ir synthetic derivatives are potent positive allosteric modulators (PAMs) of GABA(A) receptors (GABA(

200 generation GluN2C/D-selective NMDAR-positive allosteric modulators (PAMs) with a dihydropyrrolo[1,2-a

201 Most GPCR AAs are allosteric modulators and exhibit a broad range of pharm

202 Allosteric modulators are an intensively studied group o

203 ta demonstrating the effects of agonists and allosteric modulators at receptors where agonist binding

204 Allosteric modulators bind to sites that are remote from

205 Positive allosteric modulators of NMDARs include an endogenous ne

206 e XLIX, stevenleaf) can also act as positive allosteric modulators of P2X7.

207 ach of drug discovery based on the design of allosteric modulators of protein-protein interaction.

208 studies identify the first-known endogenous allosteric modulators of SIRT1 and characterize a LD-nuc

209 nhanced allosteric activity in this class of allosteric modulators were accounted for in our recently

210 They behaved as negative allosteric modulators, and molecular modeling studies su

211 ntibodies), which are functionally active as allosteric modulators, and solved co-crystal structures

212 nterface between subunits, for the design of allosteric modulators, appears as a privileged structure

213 NMDAR function can be augmented by positive allosteric modulators, including endogenous compounds, s

214 stimulated by fatty acids and small-molecule allosteric modulators.

215 ing human studies of mGlu5 receptor negative allosteric modulators.

216 t natural and designed soluble proteins into allosteric molecular switches useful in biodesign, sensi

217 Careful evaluation of allosteric movements must be undertaken to develop bette

218 The allosteric nanobody binding sites partially overlap with

219 A long-range allosteric network allows ligands in the extracellular b

220 the central features of the long-range CheY allosteric network between D57 phosphorylation site and

221 We have analyzed this allosteric network by means of ancestral sequence recons

222 describe the conformational dynamics of the allosteric network that underlies GPCR activation.

223 to the NADH-bound GDH activates a triangular allosteric network, interlinking the inhibitor with regu

224 TrpA and the beta-subunit TrpB via a complex allosteric network.

225 l surface loops that have been implicated in allosteric networks in related coagulation enzymes.

226 n of HPF1 with PARP1 or PARP2 is enhanced by allosteric networks that operate within the PARP protein

227 This striking sensitivity of allosteric networks to the presence of adjacent protein

228 so-called supertertiary structures, affects allosteric networks.

229 Here, we characterize the allosteric NTSR1 modulator SBI-553.

230 unds represent the first potent, non-acidic, allosteric P2X1 receptor antagonists reported to date.

231 -restricted TCRs, thereby revealing a common allosteric pathway among three unrelated TCRs.

232 The CP is dynamic, with an extensive allosteric pathway extending from one end of the molecul

233 S RP binding, or the introduction of gate or allosteric pathway mutations at one end of the barrel ca

234 nuclease, advancing our understanding of the allosteric pathway of activation.

235 an open activation gate and suggest a unique allosteric pathway that ties the selectivity filter to t

236 f the two subunits forming the homodimer and allosteric perturbations on cGMP binding.

237 Furthermore, several allosteric plasmin inhibitors based on heparin mimetics

238 One compound (NITD-434) induced an allosteric pocket at the junction of the fingers and pal

239 esidue, are crucial for the formation of the allosteric pocket.

240 er permeability (BBBP), and the targeting of allosteric pockets.

241 In summary, allosteric propagation in cooperative, dual-liganded enz

242 nation of highly processive RNA polymerases, allosteric protein transcription factors and synthetic D

243 The regulatory allosteric region identified here in HDAC8 corresponds t

244 ptimally active and amenable to FBP-mediated allosteric regulation at pH(i) 7.5.

245 ting of the channel state and observation of allosteric regulation by agonist binding with MD remains

246 tein covers its functional site, is a common allosteric regulation mechanism.

247 dynamics, analyzing molecular mechanism and allosteric regulation of biological systems.

248 assembly, and reveal how filament-dependent allosteric regulation of IMPDH2 makes the enzyme less se

249 observe complete activation of 5-HT(3A), the allosteric regulation of ion gating elements by 5-HT bin

250 Further, we studied allosteric regulation of isolated GCH1 by X-ray crystall

251 that targeting the cytosolic Hsp70 system by allosteric regulation of its chaperone/co-chaperone base

252 tion; from the foundational understanding of allosteric regulation of oxygen binding in Hb in the ste

253 Engineered allosteric regulation of protein activity provides signi

254 Here we report that allosteric regulation of the serine-rich loop is mediate

255 ocated on the extracellular domain (ECD) and allosteric regulation of the transmembrane domain (TMD)

256 oited to investigate the impact of defective allosteric regulation on one-carbon metabolism.

257 erties such as cooperative ligand binding or allosteric regulation(3).

258 e relationships between protein dynamics and allosteric regulation, allowing for high-throughput mode

259 a comprehensive picture of the mechanism of allosteric regulation.

260 domains and which facilitate disorder-based allosteric regulation.

261 ology, focusing on promising applications in allosteric regulations, including the investigation of a

262 ncharacterized role for the hub domain as an allosteric regulator of kinase activity, which may provi

263 ters both SHP2 substrate specificity and its allosteric regulatory mechanism.

264 quantitative computational investigations of allosteric regulatory mechanisms in protein systems.

265 ontrast to the common view of a finely tuned allosteric residue network maintained under selection.

266 ty DNA binding, is unable to induce the same allosteric response as nickel.

267 inding to H. pylori NikR (HpNikR) induces an allosteric response favoring a conformation that can bin

268 chain polarity of these AAs trigger distinct allosteric responses in PKM2.

269 ng chimera (PROTAC) strategy that couples an allosteric, reversible PTP inhibitor with an E3 ligase t

270 of cooling agonist sensing by TRPM8 and the allosteric role of PI(4,5)P(2) in agonist binding for TR

271 approach that led to the discovery of novel allosteric RORgammat inverse agonists with a distinct is

272 was essential for alpha3beta4 nAChR subtype allosteric selectivity.

273 fficiently identify residues contributing to allosteric signal propagation in multienzyme complexes.

274 that H3K4me3 binding and transmission of an allosteric signal to RAG-1 are separable functions of th

275 d backbone dynamics, completely severing the allosteric signal yet remarkably, generating a nonallost

276 We show that allosteric signaling exhibits a high degree of functiona

277 of a single Ca(2+) is a critical mediator of allosteric signaling that dictates structural changes an

278 ace into a network of communities that allow allosteric signals to propagate along unique pathways or

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

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

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

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

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

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

285 ugh interaction with a previously unrevealed allosteric site.

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

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

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

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

290 nactive kinase conformations, or act through allosteric sites.

291 s; however, deacetylation can be enhanced by allosteric small-molecule activators.

292 dsRNA binding induces allosteric structural changes in OAS1 that reorganize it

293 data also suggest the presence of a putative allosteric substrate-binding site in a hydrophobic pocke

294 The allosteric coupling constant in K-type allosteric systems is defined as a ratio of the binding

295 atility in generating chemical diversity for allosteric targeting of RORgammat.

296 Substrate binding to ProT(QQQ) caused allosteric tightening of the affinity of most SC(1-246)

297 Recently, allosteric transcription factors (TFs) were identified a

298 importers, and the biological specificity of allosteric transcriptional regulatory proteins tasked wi

299 omain-domain interface-thereby promoting the allosteric transition that triggers ATP hydrolysis.

300 They promote key allosteric transitions that stabilize Hsp70 interaction