FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2891922284> ?p ?o ?g. }

• W2891922284 endingPage "2130" @default.
• W2891922284 startingPage "2123" @default.
• W2891922284 abstract "Angiotensin II type 1 receptor (AT1R) is the principal regulator of blood pressure in humans. The overactivation of AT1R by the stimulation of angiotensin II would result in high blood pressure. To prevent hypertension, nonpeptide “sartan” drugs, such as valsartan (VST), have been developed to competitively block the access of angiotensin II to the receptor. Nuclear magnetic resonance spectroscopy and molecular modeling studies have identified that VST in solution and in lipid micelles (a mimic membrane environment) has two distinct trans/cis conformations (VSTtrans/VSTcis) that can be transformed into each other through the isomerization of the amide bond. To date, it is still not known whether the two conformations of VST can affect the binding of AT1R with VST. To this end, the binding of AT1R with VSTtrans or VSTcis was modeled based on the recently determined crystal structures of AT1R. Molecular dynamics simulations were then performed to study the structural and dynamical differences of AT1R caused by the two conformations of VST. Simulation results show that AT1R with VSTtrans has higher structural and dynamical stabilities compared to that with VSTcis. Binding energy analysis indicates that AT1R bind more strongly with VSTtrans, and the energy difference mainly results from the contribution of van der Waals and nonpolar interactions. Detailed analyses reveal that unlike AT1R with VSTtrans, AT1R with VSTcis displays an activate-like state, which is characterized by a small outward movement of transmembrane helix 6. Due to the altered interaction with the butyl group of VST, residue Tyr87 undergoes a conformational change that causes a contraction of the pocket for VST binding. The rearrangement of AT1R is then propagated to the intracellular side of the receptor through the conformational change of residue Trp253 (the toggle switch), which results in an expansion of the pocket for G protein binding and the breakage of the hydrogen bond containing the conserved residue Arg126. These data provide insights into the activation mechanism of AT1R caused by the binding of VSTcis, which may help to design a new drug to inhibit AT1R and prevent high blood pressure." @default.
• W2891922284 created "2018-09-27" @default.
• W2891922284 creator A5004346140 @default.
• W2891922284 creator A5053801409 @default.
• W2891922284 date "2018-09-13" @default.
• W2891922284 modified "2023-09-26" @default.
• W2891922284 title "Trans and Cis Conformations of the Antihypertensive Drug Valsartan Respectively Lock the Inactive and Active-like States of Angiotensin II Type 1 Receptor: A Molecular Dynamics Study" @default.
• W2891922284 cites W1833104430 @default.
• W2891922284 cites W1991388370 @default.
• W2891922284 cites W1999976306 @default.
• W2891922284 cites W2000046288 @default.
• W2891922284 cites W2008708467 @default.
• W2891922284 cites W2009376892 @default.
• W2891922284 cites W2028370247 @default.
• W2891922284 cites W2029667189 @default.
• W2891922284 cites W2058130205 @default.
• W2891922284 cites W2060487501 @default.
• W2891922284 cites W2065283382 @default.
• W2891922284 cites W2092196707 @default.
• W2891922284 cites W2097957153 @default.
• W2891922284 cites W2110177837 @default.
• W2891922284 cites W2115409589 @default.
• W2891922284 cites W2144288821 @default.
• W2891922284 cites W2144775933 @default.
• W2891922284 cites W2156850243 @default.
• W2891922284 cites W2164113467 @default.
• W2891922284 cites W2167857702 @default.
• W2891922284 cites W2168269595 @default.
• W2891922284 cites W2183358035 @default.
• W2891922284 cites W2266688981 @default.
• W2891922284 cites W2294748937 @default.
• W2891922284 cites W2317863386 @default.
• W2891922284 cites W2318592165 @default.
• W2891922284 cites W2323104785 @default.
• W2891922284 cites W2333930218 @default.
• W2891922284 cites W2336105578 @default.
• W2891922284 cites W2463173616 @default.
• W2891922284 cites W2530261714 @default.
• W2891922284 cites W2580792129 @default.
• W2891922284 cites W2605291555 @default.
• W2891922284 cites W2616042947 @default.
• W2891922284 cites W2737729073 @default.
• W2891922284 cites W2749905431 @default.
• W2891922284 cites W2767201802 @default.
• W2891922284 cites W3145527833 @default.
• W2891922284 cites W4298090388 @default.
• W2891922284 doi "https://doi.org/10.1021/acs.jcim.8b00364" @default.
• W2891922284 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30212210" @default.
• W2891922284 hasPublicationYear "2018" @default.
• W2891922284 type Work @default.
• W2891922284 sameAs 2891922284 @default.
• W2891922284 citedByCount "7" @default.
• W2891922284 countsByYear W28919222842020 @default.
• W2891922284 countsByYear W28919222842021 @default.
• W2891922284 countsByYear W28919222842022 @default.
• W2891922284 countsByYear W28919222842023 @default.
• W2891922284 crossrefType "journal-article" @default.
• W2891922284 hasAuthorship W2891922284A5004346140 @default.
• W2891922284 hasAuthorship W2891922284A5053801409 @default.
• W2891922284 hasConcept C104849204 @default.
• W2891922284 hasConcept C118892022 @default.
• W2891922284 hasConcept C12554922 @default.
• W2891922284 hasConcept C134018914 @default.
• W2891922284 hasConcept C147597530 @default.
• W2891922284 hasConcept C170493617 @default.
• W2891922284 hasConcept C185592680 @default.
• W2891922284 hasConcept C2777387769 @default.
• W2891922284 hasConcept C2908929049 @default.
• W2891922284 hasConcept C55493867 @default.
• W2891922284 hasConcept C59593255 @default.
• W2891922284 hasConcept C71240020 @default.
• W2891922284 hasConcept C84393581 @default.
• W2891922284 hasConcept C86803240 @default.
• W2891922284 hasConceptScore W2891922284C104849204 @default.
• W2891922284 hasConceptScore W2891922284C118892022 @default.
• W2891922284 hasConceptScore W2891922284C12554922 @default.
• W2891922284 hasConceptScore W2891922284C134018914 @default.
• W2891922284 hasConceptScore W2891922284C147597530 @default.
• W2891922284 hasConceptScore W2891922284C170493617 @default.
• W2891922284 hasConceptScore W2891922284C185592680 @default.
• W2891922284 hasConceptScore W2891922284C2777387769 @default.
• W2891922284 hasConceptScore W2891922284C2908929049 @default.
• W2891922284 hasConceptScore W2891922284C55493867 @default.
• W2891922284 hasConceptScore W2891922284C59593255 @default.
• W2891922284 hasConceptScore W2891922284C71240020 @default.
• W2891922284 hasConceptScore W2891922284C84393581 @default.
• W2891922284 hasConceptScore W2891922284C86803240 @default.
• W2891922284 hasFunder F4320321001 @default.
• W2891922284 hasIssue "10" @default.
• W2891922284 hasLocation W28919222841 @default.
• W2891922284 hasLocation W28919222842 @default.
• W2891922284 hasOpenAccess W2891922284 @default.
• W2891922284 hasPrimaryLocation W28919222841 @default.
• W2891922284 hasRelatedWork W2002610357 @default.
• W2891922284 hasRelatedWork W2080111355 @default.
• W2891922284 hasRelatedWork W2128791330 @default.
• W2891922284 hasRelatedWork W2144703558 @default.
• W2891922284 hasRelatedWork W2160941210 @default.

• next