1U9X

Crystal Structure of the Cysteine Protease Human Cathepsin K in Complex with the Covalent Inhibitor NVP-ABJ688


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.171 
  • R-Value Observed: 0.171 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Novel purine nitrile derived inhibitors of the cysteine protease cathepsin K

Altmann, E.Cowan-Jacob, S.W.Missbach, M.

(2004) J Med Chem 47: 5833-5836

  • DOI: https://doi.org/10.1021/jm0493111
  • Primary Citation of Related Structures:  
    1U9V, 1U9W, 1U9X

  • PubMed Abstract: 

    Starting from the high-throughput screening hit 1a, novel cathepsin K inhibitors have been developed based on a purine scaffold. High-resolution X-ray structures of several derivatives have revealed the binding mode of these unique cysteine protease inhibitors.


  • Organizational Affiliation

    Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. eva.altmann@pharma.novartis.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cathepsin K217Homo sapiensMutation(s): 0 
EC: 3.4.22.38
UniProt & NIH Common Fund Data Resources
Find proteins for P43235 (Homo sapiens)
Explore P43235 
Go to UniProtKB:  P43235
PHAROS:  P43235
GTEx:  ENSG00000143387 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP43235
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
IHJ
Query on IHJ

Download Ideal Coordinates CCD File 
B [auth A]9-CYCLOPENTYL-6-{2-[3-(4-METHYL-PIPERAZIN-1-YL)-PROPOXY]-PHENYLAMINO}-9H-PURINE-2-CARBONITRILE
C25 H32 N8 O
VWGLHPDSAYQVRM-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
IHJ BindingDB:  1U9X IC50: 7 (nM) from 1 assay(s)
PDBBind:  1U9X IC50: 7 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.171 
  • R-Value Observed: 0.171 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.5α = 90
b = 63.5β = 90
c = 116.2γ = 90
Software Package:
Software NamePurpose
XDSdata scaling
AUTOMARdata reduction
X-PLORmodel building
X-PLORrefinement
XDSdata reduction
X-PLORphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-08-11
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description