› 1y8j

X-ray diffraction
2.25Å resolution

Crystal Structure of human NEP complexed with an imidazo[4,5-c]pyridine inhibitor

Released:
DOI: 10.2210/pdb1y8j/pdb
PDB entry 1y8j coloured by chain, front view.
PDB entry 1y8j coloured by chain, side view.
PDB entry 1y8j coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Second-Generation Inhibitors for the Metalloprotease Neprilysin Based on Bicyclic Heteroaromatic Scaffolds: Synthesis, Biological Activity, and X-ray Crystal Structure Analysis
Sahli S, Frank B, Schweizer WB, Diederich F, Blum-Kaelin D, Aebi JD, Bohm HJ, Oefner C, Dale GE
Helv. Chim. Acta 88 731-750 (2005)

Function and Biology Details

Reaction catalysed: 
Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.
Biochemical function:
Biological process:
Cellular component:
Sequence domains:
Structure domain:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-140129 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Neprilysin Chain: A
Molecule details ›
Chain: A
Length: 696 amino acids
Theoretical weight: 79.53 KDa
Source organism: Homo sapiens
Expression system: Saccharomyces cerevisiae
UniProt:
  • Canonical: P08473 (Residues: 55-750; Coverage: 93%)
Gene names: EPN, MME
Sequence domains:
Structure domains:

Ligands and Environments

4 bound ligands:
Ligand NAG 3 x NAG
Ligand ZN 1 x ZN
Ligand ACT 1 x ACT
Ligand STS 1 x STS
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ENRAF-NONIUS FR591
Spacegroup: P3221
Unit cell:
a: 107.355Å b: 107.356Å c: 112.466Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.226 0.226 0.296
Expression system: Saccharomyces cerevisiae

Quick links

Citations

4 mentions without citation

Engineering neprilysin activity and specificity to create a novel therapeutic for Alzheimer's disease.
Webster et al. (2014)
3 more