Human gamma-secretase in complex with small molecule L-685,458

Structure

electron microscopy · 4 distinct chains · 51% helix, 10% strand (DSSP).

Ligands and binding sites

• CLR · Cholesterol · ligand · 3 copies · chains C
• PC1 · 1,2-diacyl-sn-glycero-3-phosphocholine · ligand · 2 copies · chains B, C, A
• FTO · ~{tert}-butyl ~{N}-[(2~{S},3~{R},5~{R})-6-[[(2~{S})-1-[[(2~{S})-1-azanyl-1-oxidanylidene-3-phenyl-propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]amino]-3-oxidanyl-6-oxidanylidene-1-phenyl-5-(phenylmethyl) hexan-2-yl]carbamate · ligand · chains B
• NAG · 2-acetamido-2-deoxy-beta-D-glucopyranose · sugar · 18 copies · chains A, C
• BMA · beta-D-mannopyranose · sugar · 3 copies · chains A

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

Pockets

14 pockets found on a 1 Å grid, 8 with a druggability of 0.5 or more.

Interfaces

5 interfaces between chains.

• A–C · 1743 Ų buried · 9 hydrogen bonds · protein-protein
• B–C · 1699 Ų buried · 10 hydrogen bonds · protein-protein
• B–D · 1146 Ų buried · 9 hydrogen bonds · protein-protein
• A–D · 514 Ų buried · 1 hydrogen bond · protein-protein
• A–B · 461 Ų buried · 2 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 12 glycan, 4 disulfide (N-glycosylation, disulfide).

Compared structures

• 7C9I · Human gamma-secretase in complex with small molecule L-685,458 · the same entry in another collection · chain D against D, TM-score 1.00
• P49768 · AlphaFold monomer V2.0 prediction for presenilin-1 (P49768) · a predicted model of the same protein · chain B against A, TM-score 0.98
• Q92542 · AlphaFold monomer V2.0 prediction for nicastrin (Q92542) · a predicted model of the same protein · chain A against A, TM-score 0.98
• Q9NZ42 · AlphaFold monomer V2.0 prediction for gamma-secretase subunit pen-2 (Q9NZ42) · a predicted model of the same protein · chain D against A, TM-score 0.97
• Q96BI3 · AlphaFold monomer V2.0 prediction for gamma-secretase subunit aph-1A (Q96BI3) · a predicted model of the same protein · chain C against A, TM-score 0.97

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 Q92542
• Every structure of UniProt P49768
• Every structure of UniProt Q96BI3
• Every structure of UniProt Q9NZ42
• Elsewhere: RCSB PDB 7C9I · PDBe 7C9I · UniProt Q92542 · UniProt P49768 · UniProt Q96BI3 · UniProt Q9NZ42