8FD7

Structure of the human L-type voltage-gated calcium channel Cav1.2 complexed with gabapentin

Summary for 8FD7

• Entry DOI: 10.2210/pdb8fd7/pdb
• EMDB information: 29004 29006 29007 29015
• Descriptor: Voltage-dependent calcium channel subunit alpha-2/delta-1, (2S)-3-{[(R)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-2-(dodecanoyloxy)propyl dodecanoate, CHOLESTEROL, ... (12 entities in total)
• Functional Keywords: voltage-gated calcium channel, cav alpha2delta, drug binding, gabapentin, membrane protein
• Biological source: Oryctolagus cuniculus (rabbit); More
• Total number of polymer chains: 3
• Total formula weight: 370952.36

Authors

Chen, Z.,Mondal, A.,Minor, D.L. (deposition date: 2022-12-02, release date: 2023-03-22, Last modification date: 2024-10-23)

Primary citation

Chen, Z.,Mondal, A.,Minor Jr., D.L.
Structural basis for Ca V alpha 2 delta :gabapentin binding.
Nat.Struct.Mol.Biol., 30:735-739, 2023

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-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.

PubMed: 36973510
DOI: 10.1038/s41594-023-00951-7

Experimental method

ELECTRON MICROSCOPY (3.1 Å)