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Title | Structural basis for Caαδ:gabapentin binding. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 30, Issue 6, Page 735-739, Year 2023 |
Publish date | Mar 27, 2023 |
Authors | Zhou Chen / Abhisek Mondal / Daniel L Minor / |
PubMed Abstract | Gabapentinoid drugs for pain and anxiety act on the Caαδ-1 and Caαδ-2 subunits of high-voltage-activated calcium channels (Ca1s and Ca2s). Here we present the cryo-EM structure of the gabapentin- ...Gabapentinoid drugs for pain and anxiety act on the Caαδ-1 and Caαδ-2 subunits of high-voltage-activated calcium channels (Ca1s and Ca2s). Here we present the cryo-EM structure of the gabapentin-bound brain and cardiac Ca1.2/Caβ/Caαδ-1 channel. The data reveal a binding pocket in the Caαδ-1 dCache1 domain that completely encapsulates gabapentin and define Caαδ isoform sequence variations that explain the gabapentin binding selectivity of Caαδ-1 and Caαδ-2. |
External links | Nat Struct Mol Biol / PubMed:36973510 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.1 Å |
Structure data | EMDB-29004, PDB-8fd7: EMDB-29006: human EMC:human Cav1.2 channel complex in GDN detergent at 3.1 Angstrom EMDB-29007: Human L-type voltage-gated calcium channel Cav1.2 complexed with gabapentin (Segment Map) EMDB-29015: Structure of the human L-type voltage-gated calcium channel Cav1.2 complexed with gabapentin (consensus map) |
Chemicals | ChemComp-NAG: ChemComp-GBN: ChemComp-CA: ChemComp-NA: ChemComp-WO9: ChemComp-YSW: ChemComp-CLR: ChemComp-HOH: |
Source |
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Keywords | MEMBRANE PROTEIN / voltage-gated calcium channel / CaV alpha2delta / drug binding / gabapentin |