› 4cdf

X-ray diffraction
2.2Å resolution

Human DPP1 in complex with (2S,4S)-N-((1S)-1-cyano-2-(4-(4- cyanophenyl)phenyl)ethyl)-4-hydroxy-piperidine-2-carboxamide

Released:
DOI: 10.2210/pdb4cdf/pdb
PDB entry 4cdf coloured by chain, front view.
PDB entry 4cdf coloured by chain, side view.
PDB entry 4cdf coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Cathepsin C inhibitors: property optimization and identification of a clinical candidate.
Furber M, Tiden AK, Gardiner P, Mete A, Ford R, Millichip I, Stein L, Mather A, Kinchin E, Luckhurst C, Barber S, Cage P, Sanganee H, Austin R, Chohan K, Beri R, Thong B, Wallace A, Oreffo V, Hutchinson R, Harper S, Debreczeni J, Breed J, Wissler L, Edman K
J Med Chem 57 2357-67 (2014)
PMID: 24592859

Function and Biology Details

Reaction catalysed: 
Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, except when Xaa is Arg or Lys, or Yaa or Zaa is Pro.
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
hetero trimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-156841 (preferred)
Entry contents:
3 distinct polypeptide molecules
Macromolecules (3 distinct):
Dipeptidyl peptidase 1 exclusion domain chain Chains: A, D
Molecule details ›
Chains: A, D
Length: 120 amino acids
Theoretical weight: 13.6 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P53634 (Residues: 25-144; Coverage: 27%)
Gene names: CPPI, CTSC
Sequence domains: Cathepsin C exclusion domain
Structure domains: Cathepsin C, exclusion domain
Dipeptidyl peptidase 1 heavy chain Chains: B, E
Molecule details ›
Chains: B, E
Length: 166 amino acids
Theoretical weight: 18.74 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P53634 (Residues: 229-394; Coverage: 38%)
Gene names: CPPI, CTSC
Sequence domains: Papain family cysteine protease
Structure domains: Cysteine proteinases
Dipeptidyl peptidase 1 light chain Chains: C, F
Molecule details ›
Chains: C, F
Length: 69 amino acids
Theoretical weight: 7.58 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P53634 (Residues: 395-463; Coverage: 16%)
Gene names: CPPI, CTSC
Structure domains: Cysteine proteinases. Chain C

Ligands and Environments

3 bound ligands:
Ligand NAG 4 x NAG
Ligand W2C 2 x W2C
Ligand CL 2 x CL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF
Spacegroup: P3121
Unit cell:
a: 84.85Å b: 84.85Å c: 222.452Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.219 0.217 0.255
Expression system: Spodoptera frugiperda

Quick links

Citations

3 review citations

Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors.
Siklos et al. (2015)
2 more

1 mention without citation

DPP1 Inhibitors: Exploring the Role of Water in the S2 Pocket of DPP1 with Substituted Pyrrolidines.
Käck et al. (2019)