› 8cgp

X-ray diffraction
2.62Å resolution

Insulin regulated aminopeptidase (IRAP) in complex with an allosteric aryl sulfonamide inhibitor

Released:
DOI: 10.2210/pdb8cgp/pdb
PDB entry 8cgp coloured by chain, front view.
PDB entry 8cgp coloured by chain, side view.
PDB entry 8cgp coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Mechanisms of allosteric inhibition of Insulin-Regulated Aminopeptidase.
Mpakali A, Barla I, Lu L, Ramesh KM, Thomaidis N, Stern LJ, Giastas P, Stratikos E
J Mol Biol 168449 (2024)
PMID: 38244767

Function and Biology Details

Reaction catalysed: 
Release of an N-terminal amino acid, Cys-|-Xaa-, in which the half-cystine residue is involved in a disulfide loop, notably in oxytocin or vasopressin. Hydrolysis rates on a range of aminoacyl arylamides exceed that for the cystinyl derivative, however.
Biochemical function:
Biological process:
Cellular component:
  • not assigned

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-193794 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecules (8 distinct):
Leucyl-cystinyl aminopeptidase, pregnancy serum form Chains: A, B
Molecule details ›
Chains: A, B
Length: 873 amino acids
Theoretical weight: 100.4 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q9UIQ6 (Residues: 155-1025; Coverage: 85%)
Gene names: LNPEP, OTASE
Sequence domains:

Ligands and Environments

Carbohydrate polymer : NEW Components: NAG, BMA, MAN
Carbohydrate polymer
Carbohydrate polymer : NEW Components: NAG
Carbohydrate polymer
Carbohydrate polymer : NEW Components: NAG, BMA, MAN
Carbohydrate polymer
Carbohydrate polymer : NEW Components: NAG, BMA, MAN
Carbohydrate polymer
Carbohydrate polymer : NEW Components: NAG, BMA
Carbohydrate polymer
Carbohydrate polymer : NEW Components: NAG, BMA, MAN
Carbohydrate polymer
Carbohydrate polymer : NEW Components: NAG, BMA, MAN
Carbohydrate polymer
6 bound ligands:
Ligand NAG 7 x NAG
Ligand MLT 2 x MLT
Ligand ZN 2 x ZN
Ligand UKG 2 x UKG
Ligand PEG 2 x PEG
Ligand EDO 4 x EDO
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: PETRA III, EMBL c/o DESY BEAMLINE P13 (MX1)
Spacegroup: P21
Unit cell:
a: 73.443Å b: 119.074Å c: 141.643Å
α: 90° β: 102.77° γ: 90°
R-values:
R R work R free
0.17 0.17 0.231
Expression system: Homo sapiens

Quick links

Citations

2 citation in other articles

Stabilization of the open conformation οf insulin-regulated aminopeptidase by a novel substrate-selective small-molecule inhibitor.
Mpakali et al. (2024)
1 more