Matches in SemOpenAlex for { <https://semopenalex.org/work/W4246305424> ?p ?o ?g. }
Showing items 1 to 72 of
72
with 100 items per page.
- W4246305424 abstract "<p>Small molecule kinase inhibitors that stabilize distinct ATP-binding site conformations can differentially modulate the glob-al conformation of Src-family kinases (SFKs). However, it is unclear which specific ATP-binding site contacts are responsible for modulating the global conformation of SFKs and whether these inhibitor-mediated allosteric effects are general to other tyrosine kinases. Here, we describe the development of chemical probes that allow us to deconvolute which features in the ATP-binding site are responsible for the allosteric modulation of the global conformation of Src. We find that the ability of an inhibitor to modulate the global conformation of Src’s regulatory domain-catalytic domain module relies mainly on the influence it has on the conformation of a structural element called helix aC. Furthermore, by developing a set of orthogonal probes that target a drug-sensitized Src variant, we show that stabilizing Src’s helix aC in an active conformation is sufficient to promote a Src-mediated, phosphotransferase-independent alteration in cell morphology. Finally, we report that ATP-competitive, conformation-selective inhibitors can influence the global conformation of tyrosine kinases beyond the SFKs, suggesting that the allosteric networks we observe in Src are conserved in kinases that have a similar regulatory architecture. Taken together, our study highlights that an ATP-competitive inhibitor’s interactions with helix aC can have a major influence on the global conformation of some tyrosine kinases in vitro and in cells.</p>" @default.
- W4246305424 created "2022-05-12" @default.
- W4246305424 creator A5003432548 @default.
- W4246305424 creator A5007812813 @default.
- W4246305424 creator A5008590226 @default.
- W4246305424 creator A5014219228 @default.
- W4246305424 creator A5054397869 @default.
- W4246305424 creator A5060345055 @default.
- W4246305424 creator A5082101583 @default.
- W4246305424 date "2020-04-23" @default.
- W4246305424 modified "2023-09-28" @default.
- W4246305424 title "How ATP-Competitive Inhibitors Allosterically Modulate Tyrosine Kinases That Contain a Src-like Regulatory Architecture" @default.
- W4246305424 doi "https://doi.org/10.26434/chemrxiv.12148524.v2" @default.
- W4246305424 hasPublicationYear "2020" @default.
- W4246305424 type Work @default.
- W4246305424 citedByCount "0" @default.
- W4246305424 crossrefType "posted-content" @default.
- W4246305424 hasAuthorship W4246305424A5003432548 @default.
- W4246305424 hasAuthorship W4246305424A5007812813 @default.
- W4246305424 hasAuthorship W4246305424A5008590226 @default.
- W4246305424 hasAuthorship W4246305424A5014219228 @default.
- W4246305424 hasAuthorship W4246305424A5054397869 @default.
- W4246305424 hasAuthorship W4246305424A5060345055 @default.
- W4246305424 hasAuthorship W4246305424A5082101583 @default.
- W4246305424 hasBestOaLocation W42463054241 @default.
- W4246305424 hasConcept C101544691 @default.
- W4246305424 hasConcept C108636557 @default.
- W4246305424 hasConcept C161624437 @default.
- W4246305424 hasConcept C166342909 @default.
- W4246305424 hasConcept C181199279 @default.
- W4246305424 hasConcept C183141693 @default.
- W4246305424 hasConcept C184235292 @default.
- W4246305424 hasConcept C185592680 @default.
- W4246305424 hasConcept C196347352 @default.
- W4246305424 hasConcept C197153747 @default.
- W4246305424 hasConcept C42362537 @default.
- W4246305424 hasConcept C55493867 @default.
- W4246305424 hasConcept C62478195 @default.
- W4246305424 hasConcept C86803240 @default.
- W4246305424 hasConcept C95444343 @default.
- W4246305424 hasConceptScore W4246305424C101544691 @default.
- W4246305424 hasConceptScore W4246305424C108636557 @default.
- W4246305424 hasConceptScore W4246305424C161624437 @default.
- W4246305424 hasConceptScore W4246305424C166342909 @default.
- W4246305424 hasConceptScore W4246305424C181199279 @default.
- W4246305424 hasConceptScore W4246305424C183141693 @default.
- W4246305424 hasConceptScore W4246305424C184235292 @default.
- W4246305424 hasConceptScore W4246305424C185592680 @default.
- W4246305424 hasConceptScore W4246305424C196347352 @default.
- W4246305424 hasConceptScore W4246305424C197153747 @default.
- W4246305424 hasConceptScore W4246305424C42362537 @default.
- W4246305424 hasConceptScore W4246305424C55493867 @default.
- W4246305424 hasConceptScore W4246305424C62478195 @default.
- W4246305424 hasConceptScore W4246305424C86803240 @default.
- W4246305424 hasConceptScore W4246305424C95444343 @default.
- W4246305424 hasLocation W42463054241 @default.
- W4246305424 hasLocation W42463054242 @default.
- W4246305424 hasOpenAccess W4246305424 @default.
- W4246305424 hasPrimaryLocation W42463054241 @default.
- W4246305424 hasRelatedWork W2019597715 @default.
- W4246305424 hasRelatedWork W2047465993 @default.
- W4246305424 hasRelatedWork W2048000913 @default.
- W4246305424 hasRelatedWork W2345629930 @default.
- W4246305424 hasRelatedWork W2396138891 @default.
- W4246305424 hasRelatedWork W2460715479 @default.
- W4246305424 hasRelatedWork W2912079091 @default.
- W4246305424 hasRelatedWork W3029756893 @default.
- W4246305424 hasRelatedWork W4241010438 @default.
- W4246305424 hasRelatedWork W4246305424 @default.
- W4246305424 isParatext "false" @default.
- W4246305424 isRetracted "false" @default.
- W4246305424 workType "article" @default.