3OVZ

Cathepsin K in complex with a covalent inhibitor with a ketoamide warhead


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.02 Å
  • R-Value Free: 0.308 
  • R-Value Work: 0.244 
  • R-Value Observed: 0.247 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Trifluoromethylphenyl as P2 for ketoamide-based cathepsin S inhibitors.

Cai, J.Robinson, J.Belshaw, S.Everett, K.Fradera, X.van Zeeland, M.van Berkom, L.van Rijnsbergen, P.Popplestone, L.Baugh, M.Dempster, M.Bruin, J.Hamilton, W.Kinghorn, E.Westwood, P.Kerr, J.Rankovic, Z.Arbuckle, W.Bennett, D.J.Jones, P.S.Long, C.Martin, I.Uitdehaag, J.C.Meulemans, T.

(2010) Bioorg Med Chem Lett 20: 6890-6894

  • DOI: https://doi.org/10.1016/j.bmcl.2010.10.012
  • Primary Citation of Related Structures:  
    3OVX, 3OVZ

  • PubMed Abstract: 

    The trifluoromethylphenyl P2 motif from previously reported heteroarylnitrile series has been successfully applied for the design and synthesis of highly potent novel ketoamide-based cathepsin S inhibitors. The key in this process is the change of the torsion angle between the P2 phenyl ring and the attached secondary amide by adding a small Cl, F, or Me group at the 2-position.


  • Organizational Affiliation

    Merck Research Laboratories, MSD, Newhouse, Lanarkshire, United Kingdom. jiaqiang.cai@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cathepsin K213Homo sapiensMutation(s): 0 
Gene Names: CTSKCTSOCTSO2
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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
O96
Query on O96

Download Ideal Coordinates CCD File 
B [auth A]N-[(1S)-3-amino-1-ethyl-2,3-dioxopropyl]-2-chloro-4-(pyridin-2-ylmethoxy)-3-(trifluoromethyl)benzamide
C19 H17 Cl F3 N3 O4
VMSZYKRQEOLBRN-LBPRGKRZSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
O96 BindingDB:  3OVZ IC50: 8.7 (nM) from 1 assay(s)
PDBBind:  3OVZ IC50: 8.7 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.02 Å
  • R-Value Free: 0.308 
  • R-Value Work: 0.244 
  • R-Value Observed: 0.247 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.741α = 90
b = 55.741β = 90
c = 128.916γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
MOLREPphasing
REFMACrefinement
d*TREKdata reduction
d*TREKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-12-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-10-12
    Changes: Derived calculations
  • Version 1.3: 2012-05-09
    Changes: Data collection
  • Version 1.4: 2018-01-31
    Changes: Experimental preparation