› 6eds

X-ray diffraction
3.18Å resolution

Structure of Cysteine-free Human Insulin-Degrading Enzyme in complex with Glucagon and Substrate-selective Macrocyclic Inhibitor 63

Released:
DOI: 10.2210/pdb6eds/pdb
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PDB entry 6eds coloured by chain, front view.
PDB entry 6eds coloured by chain, side view.
PDB entry 6eds coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Substrate-selective inhibitors that reprogram the activity of insulin-degrading enzyme.
Maianti JP, Tan GA, Vetere A, Welsh AJ, Wagner BK, Seeliger MA, Liu DR
OpenAccess logo Nat Chem Biol 15 565-574 (2019)
PMID: 31086331

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-134155 (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
Glucagon Chains: C, D
Molecule details ›
Chains: C, D
Length: 29 amino acids
Theoretical weight: 3.49 KDa
Source organism: Homo sapiens
Expression system: Saccharomyces cerevisiae
UniProt:
  • Canonical: P01275 (Residues: 53-81; Coverage: 18%)
Gene name: GCG
Sequence domains: Peptide hormone

Ligands and Environments

4 bound ligands:
Ligand J22 2 x J22
Ligand EPE 2 x EPE
Ligand PEG 2 x PEG
Ligand DIO 2 x DIO
No modified residues

Experiments and Validation Details

wwPDB Validation report is not available for this entry.
X-ray source: NSLS-II BEAMLINE 17-ID-2
Spacegroup: P65
Unit cell:
a: 263.119Å b: 263.119Å c: 90.322Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.179 0.177 0.222
Expression systems:
  • Escherichia coli BL21(DE3)
  • Saccharomyces cerevisiae

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Citations

9 review citations

Targeting Insulin-Degrading Enzyme in Insulin Clearance.
Leissring et al. (2021)
8 more

3 mentions without citation

Substrate-selective inhibitors that reprogram the activity of insulin-degrading enzyme.
Maianti et al. (2019)
2 more

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