› 4lte

X-ray diffraction
2.7Å resolution

Structure of Cysteine-free Human Insulin Degrading Enzyme in Complex with Macrocyclic Inhibitor

Released:
DOI: 10.2210/pdb4lte/pdb
PDB entry 4lte coloured by chain, front view.
PDB entry 4lte coloured by chain, side view.
PDB entry 4lte coloured by chain, top view.
Source organisms:
Primary publication:
Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones.
Maianti JP, McFedries A, Foda ZH, Kleiner RE, Du XQ, Leissring MA, Tang WJ, Charron MJ, Seeliger MA, Saghatelian A, Liu DR
Nature 511 94-8 (2014)
PMID: 24847884

Function and Biology Details

Reaction catalysed: 
Degradation of insulin, glucagon and other polypeptides. No action on proteins.
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-147041 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Insulin-degrading enzyme Chains: A, B
Molecule details ›
Chains: A, B
Length: 978 amino acids
Theoretical weight: 113.19 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P14735 (Residues: 42-1019; Coverage: 96%)
Gene name: IDE
Sequence domains:
Structure domains: Metalloenzyme, LuxS/M16 peptidase-like
Macrocyclic Inhibitor Chains: M, N
Molecule details ›
Chains: M, N
Length: 3 amino acids
Theoretical weight: 545 Da
Source organism: synthetic construct
Expression system: Not provided

Ligands and Environments

4 bound ligands:
Ligand ZN 2 x ZN
Ligand EPE 2 x EPE
Ligand LYN 2 x LYN
Ligand FUM 2 x FUM
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X29A
Spacegroup: P65
Unit cell:
a: 261.973Å b: 261.973Å c: 90.775Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.158 0.158 0.2
Expression systems:
  • Escherichia coli BL21(DE3)
  • Not provided

Quick links

Citations

40 review citations

DNA-encoded chemistry: enabling the deeper sampling of chemical space.
Goodnow et al. (2017)
39 more

3 mentions without citation

Targeting Insulin-Degrading Enzyme to Treat Type 2 Diabetes Mellitus.
Tang WJ. (2016)
2 more