› 7y5x

Electron Microscopy
3Å resolution

CryoEM structure of PS2-containing gamma-secretase treated with MRK-560

Released:
DOI: 10.2210/pdb7y5x/pdb
PDB entry 7y5x coloured by chain, front view.
PDB entry 7y5x coloured by chain, side view.
PDB entry 7y5x coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Molecular basis for isoform-selective inhibition of presenilin-1 by MRK-560.
Guo X, Wang Y, Zhou J, Jin C, Wang J, Jia B, Jing D, Yan C, Lei J, Zhou R, Shi Y
Nat Commun 13 6299 (2022)
PMID: 36272978
Related structures: EMD-33628

Function and Biology Details

Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-156052 (preferred)
Entry contents:
4 distinct polypeptide molecules
Macromolecules (6 distinct):
Nicastrin Chain: A
Molecule details ›
Chain: A
Length: 709 amino acids
Theoretical weight: 78.48 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q92542 (Residues: 1-709; Coverage: 100%)
Gene names: KIAA0253, NCSTN, UNQ1874/PRO4317
Sequence domains:
Presenilin-2 Chain: B
Molecule details ›
Chain: B
Length: 448 amino acids
Theoretical weight: 50.17 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P49810 (Residues: 1-448; Coverage: 100%)
Gene names: AD4, PS2, PSEN2, PSNL2, STM2
Sequence domains: Presenilin
Gamma-secretase subunit APH-1A Chain: C
Molecule details ›
Chain: C
Length: 265 amino acids
Theoretical weight: 29.02 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q96BI3 (Residues: 1-265; Coverage: 100%)
Gene names: APH1A, CGI-78, PSF, UNQ579/PRO1141
Sequence domains: Aph-1 protein
Gamma-secretase subunit PEN-2 Chain: D
Molecule details ›
Chain: D
Length: 101 amino acids
Theoretical weight: 12.04 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q9NZ42 (Residues: 1-101; Coverage: 100%)
Gene names: MDS033, PEN2, PSENEN
Sequence domains: Presenilin enhancer-2 subunit of gamma secretase

Ligands and Environments

Carbohydrate polymer : NEW Components: NAG
Carbohydrate polymer
Carbohydrate polymer : NEW Components: NAG, BMA
Carbohydrate polymer
3 bound ligands:
Ligand NAG 6 x NAG
Ligand PC1 2 x PC1
Ligand CLR 3 x CLR
No modified residues

Experiments and Validation Details

Entry percentile scores
Resolution: 3Å
Relevant EMDB volumes: EMD-33628
Expression system: Homo sapiens

Quick links

Citations

3 citation in other articles

Different transmembrane domains determine the specificity and efficiency of the cleavage activity of the γ-secretase subunit presenilin.
Schmidt et al. (2023)
2 more