Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313199013> ?p ?o ?g. }
Showing items 1 to 81 of
81
with 100 items per page.
- W4313199013 endingPage "009" @default.
- W4313199013 startingPage "1" @default.
- W4313199013 abstract "Mirogabalin is a novel gabapentinoid drug, following gabapentin and pregabalin, and given as a first-line agent for peripheral neuropathic pain. Mirogabalin is a γ-aminobutyric acid analog that binds to the voltage-gated calcium channel subunit α2δ1. However, the mirogabalin recognition mechanism of α2δ1 remains elusive. Here we analyzed a structure of recombinant human α2δ1 bound to mirogabalin at 3.88 Å resolution by cryo-electron microscopy. Our structure and mutagenesis binding assays confirmed that the evidence shown by others for gabapentinoid binding to a conserved amino acid binding motif located in the extracellular dCache_1 domain distal pocket applies to mirogabalin. In addition to the conserved residues interacting with the carboxyl and amino groups of mirogabalin, our mutagenesis binding assays newly identified residues W205 and Y217 in the hydrophobic interaction region are critical for mirogabalin binding. The A215L mutation, which was introduced to increase the side chain length at the hydrophobic interaction site of mirogabalin based on our structure, predictably suppressed the binding of mirogabalin while promoting the binding of another ligand, L-Leu, with a smaller hydrophobic substituent than mirogabalin. Our study indicates the significance of hydrophobic interactions in α2δ1 mirogabalin recognition." @default.
- W4313199013 created "2023-01-06" @default.
- W4313199013 creator A5007145673 @default.
- W4313199013 creator A5009271577 @default.
- W4313199013 creator A5022487976 @default.
- W4313199013 creator A5025185144 @default.
- W4313199013 creator A5025207906 @default.
- W4313199013 creator A5030872199 @default.
- W4313199013 creator A5051338653 @default.
- W4313199013 creator A5060489200 @default.
- W4313199013 creator A5063520009 @default.
- W4313199013 creator A5067133587 @default.
- W4313199013 creator A5076658766 @default.
- W4313199013 creator A5081118215 @default.
- W4313199013 date "2022-01-01" @default.
- W4313199013 modified "2023-10-16" @default.
- W4313199013 title "The recognition mechanism of the analgesic drug mirogabalin by recombinant human α<sub>2</sub>δ1 protein" @default.
- W4313199013 doi "https://doi.org/10.1254/jpssuppl.96.0_1-b-p-009" @default.
- W4313199013 hasPublicationYear "2022" @default.
- W4313199013 type Work @default.
- W4313199013 citedByCount "0" @default.
- W4313199013 crossrefType "journal-article" @default.
- W4313199013 hasAuthorship W4313199013A5007145673 @default.
- W4313199013 hasAuthorship W4313199013A5009271577 @default.
- W4313199013 hasAuthorship W4313199013A5022487976 @default.
- W4313199013 hasAuthorship W4313199013A5025185144 @default.
- W4313199013 hasAuthorship W4313199013A5025207906 @default.
- W4313199013 hasAuthorship W4313199013A5030872199 @default.
- W4313199013 hasAuthorship W4313199013A5051338653 @default.
- W4313199013 hasAuthorship W4313199013A5060489200 @default.
- W4313199013 hasAuthorship W4313199013A5063520009 @default.
- W4313199013 hasAuthorship W4313199013A5067133587 @default.
- W4313199013 hasAuthorship W4313199013A5076658766 @default.
- W4313199013 hasAuthorship W4313199013A5081118215 @default.
- W4313199013 hasBestOaLocation W43131990131 @default.
- W4313199013 hasConcept C107824862 @default.
- W4313199013 hasConcept C118552586 @default.
- W4313199013 hasConcept C12554922 @default.
- W4313199013 hasConcept C142724271 @default.
- W4313199013 hasConcept C185592680 @default.
- W4313199013 hasConcept C204787440 @default.
- W4313199013 hasConcept C2776468701 @default.
- W4313199013 hasConcept C2776608144 @default.
- W4313199013 hasConcept C515207424 @default.
- W4313199013 hasConcept C51639874 @default.
- W4313199013 hasConcept C55493867 @default.
- W4313199013 hasConcept C71924100 @default.
- W4313199013 hasConcept C86803240 @default.
- W4313199013 hasConceptScore W4313199013C107824862 @default.
- W4313199013 hasConceptScore W4313199013C118552586 @default.
- W4313199013 hasConceptScore W4313199013C12554922 @default.
- W4313199013 hasConceptScore W4313199013C142724271 @default.
- W4313199013 hasConceptScore W4313199013C185592680 @default.
- W4313199013 hasConceptScore W4313199013C204787440 @default.
- W4313199013 hasConceptScore W4313199013C2776468701 @default.
- W4313199013 hasConceptScore W4313199013C2776608144 @default.
- W4313199013 hasConceptScore W4313199013C515207424 @default.
- W4313199013 hasConceptScore W4313199013C51639874 @default.
- W4313199013 hasConceptScore W4313199013C55493867 @default.
- W4313199013 hasConceptScore W4313199013C71924100 @default.
- W4313199013 hasConceptScore W4313199013C86803240 @default.
- W4313199013 hasIssue "0" @default.
- W4313199013 hasLocation W43131990131 @default.
- W4313199013 hasOpenAccess W4313199013 @default.
- W4313199013 hasPrimaryLocation W43131990131 @default.
- W4313199013 hasRelatedWork W1603789301 @default.
- W4313199013 hasRelatedWork W1982354147 @default.
- W4313199013 hasRelatedWork W2018235755 @default.
- W4313199013 hasRelatedWork W2059584638 @default.
- W4313199013 hasRelatedWork W2085955934 @default.
- W4313199013 hasRelatedWork W2102146936 @default.
- W4313199013 hasRelatedWork W2427998189 @default.
- W4313199013 hasRelatedWork W2497317198 @default.
- W4313199013 hasRelatedWork W3120063484 @default.
- W4313199013 hasRelatedWork W85920738 @default.
- W4313199013 hasVolume "96" @default.
- W4313199013 isParatext "false" @default.
- W4313199013 isRetracted "false" @default.
- W4313199013 workType "article" @default.