Cryo-EM structure of human TRPC6 in complex with antagonist am-1473

Structure

electron microscopy · 1 distinct chain · 57% helix, 1% strand (DSSP).

Ligands and binding sites

• Y01 · Cholesterol hemisuccinate · ligand · 8 copies · chains A, B, D, C
• R0G · 4-({(1R,2R)-2-[(3R)-3-aminopiperidin-1-yl]-2,3-dihydro-1H-inden-1-yl}oxy)benzonitrile · ligand · 4 copies · chains A, B, C, D
• S9Y · 2-[[(2~{S})-2-decanoyloxypropoxy]-oxidanyl-phosphoryl]oxyethyl-trimethyl-azanium · ligand · 4 copies · chains A, B, C, D
• SBJ · [(2~{S})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-octanoyloxy-propan-2-yl] octadecanoate · ligand · 4 copies · chains A, B, D, C

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

20 pockets found on a 1 Å grid, 20 with a druggability of 0.5 or more.

Interfaces

6 interfaces between chains.

• A–B · 4633 Ų buried · 28 hydrogen bonds · protein-protein
• B–C · 4616 Ų buried · 28 hydrogen bonds · protein-protein
• A–D · 4610 Ų buried · 28 hydrogen bonds · protein-protein
• C–D · 4600 Ų buried · 28 hydrogen bonds · protein-protein
• B–D · 70 Ų buried · 0 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 4 disulfide (disulfide).

Compared structures

• 6UZA · Cryo-EM structure of human TRPC6 in complex with antagonist AM-1473 · the same entry in another collection · chain A against A, TM-score 1.00
• Q9Y210 · AlphaFold monomer V2.0 prediction for short transient receptor potential channel 6… · a predicted model of the same protein · chain A against A, TM-score 0.91

Analyse

• Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
• Every structure of UniProt Q9Y210
• Elsewhere: RCSB PDB 6UZA · PDBe 6UZA · UniProt Q9Y210