2DJF

Crystal Structure of human dipeptidyl peptidase I (Cathepsin C) in complex with the inhibitor Gly-Phe-CHN2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.161 
  • R-Value Observed: 0.163 

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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2

Molgaard, A.Arnau, J.Lauritzen, C.Larsen, S.Petersen, G.Pedersen, J.

(2007) Biochem J 401: 645-650

  • DOI: https://doi.org/10.1042/BJ20061389
  • Primary Citation of Related Structures:  
    2DJF, 2DJG

  • PubMed Abstract: 

    hDDPI (human dipeptidyl peptidase I) is a lysosomal cysteine protease involved in zymogen activation of granule-associated proteases, including granzymes A and B from cytotoxic T-lymphocytes and natural killer cells, cathepsin G and neutrophil elastase, and mast cell tryptase and chymase. In the present paper, we provide the first crystal structure of an hDPPI-inhibitor complex. The inhibitor Gly-Phe-CHN2 (Gly-Phe-diazomethane) was co-crystallized with hDPPI and the structure was determined at 2.0 A (1 A=0.1 nm) resolution. The structure of the native enzyme was also determined to 2.05 A resolution to resolve apparent discrepancies between the complex structure and the previously published structure of the native enzyme. The new structure of the native enzyme is, within the experimental error, identical with the structure of the enzyme-inhibitor complex presented here. The inhibitor interacts with three subunits of hDPPI, and is covalently bound to Cys234 at the active site. The interaction between the totally conserved Asp1 of hDPPI and the ammonium group of the inhibitor forms an essential interaction that mimics enzyme-substrate interactions. The structure of the inhibitor complex provides an explanation of the substrate specificity of hDPPI, and gives a background for the design of new inhibitors.


  • Organizational Affiliation

    Centre for Crystallographic Studies, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen Ø, Denmark. anne@ccs.ki.ku.dk


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dipeptidyl-peptidase 1119Homo sapiensMutation(s): 0 
Gene Names: CTSC
EC: 3.4.14.1
UniProt & NIH Common Fund Data Resources
Find proteins for P53634 (Homo sapiens)
Explore P53634 
Go to UniProtKB:  P53634
PHAROS:  P53634
GTEx:  ENSG00000109861 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP53634
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Dipeptidyl-peptidase 1164Homo sapiensMutation(s): 0 
Gene Names: CTSC
EC: 3.4.14.1
UniProt & NIH Common Fund Data Resources
Find proteins for P53634 (Homo sapiens)
Explore P53634 
Go to UniProtKB:  P53634
PHAROS:  P53634
GTEx:  ENSG00000109861 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP53634
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Dipeptidyl-peptidase 169Homo sapiensMutation(s): 0 
Gene Names: CTSC
EC: 3.4.14.1
UniProt & NIH Common Fund Data Resources
Find proteins for P53634 (Homo sapiens)
Explore P53634 
Go to UniProtKB:  P53634
PHAROS:  P53634
GTEx:  ENSG00000109861 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP53634
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
1ZB
Query on 1ZB

Download Ideal Coordinates CCD File 
J [auth B]N-[(1S)-1-benzyl-3-diazen-1-iumylidene-2-oxopropyl]glycinamide
C12 H14 N4 O2
CBOIZHHBFFTMCQ-JTQLQIEISA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A],
H [auth B]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
ACY
Query on ACY

Download Ideal Coordinates CCD File 
G [auth A]ACETIC ACID
C2 H4 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
I [auth B]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.161 
  • R-Value Observed: 0.163 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 87α = 90
b = 89.03β = 90
c = 115.57γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-11-14
    Type: Initial release
  • Version 1.1: 2007-12-26
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Structure summary, Version format compliance
  • Version 1.3: 2018-05-23
    Changes: Advisory, Data collection
  • Version 1.4: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.5: 2023-10-25
    Changes: Data collection, Database references, Refinement description, Structure summary