2AUZ

Cathepsin K complexed with a semicarbazone inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.193 

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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors?

Adkison, K.K.Barrett, D.G.Deaton, D.N.Gampe, R.T.Hassell, A.M.Long, S.T.McFadyen, R.B.Miller, A.B.Miller, L.R.Payne, J.A.Shewchuk, L.M.Wells-Knecht, K.J.Willard, D.H.Wright, L.L.

(2006) Bioorg Med Chem Lett 16: 978-983

  • DOI: https://doi.org/10.1016/j.bmcl.2005.10.108
  • Primary Citation of Related Structures:  
    2AUX, 2AUZ

  • PubMed Abstract: 

    Starting from potent aldehyde inhibitors with poor drug properties, derivatization to semicarbazones led to the identification of a series of semicarbazone-based cathepsin K inhibitors with greater solubility and better pharmacokinetic profiles than their parent aldehydes. Furthermore, a representative semicarbazone inhibitor attenuated bone resorption in an ex vivo rat calvarial bone resorption model. However, based on enzyme inhibition comparisons at neutral pH, semicarbazone hydrolysis rates, and 13C NMR experiments, these semicarbazones probably function as prodrugs of aldehydes.


  • Organizational Affiliation

    Department of Research Bioanalysis and Drug Metabolism, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cathepsin K215Homo 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
Binding Affinity Annotations 
IDSourceBinding Affinity
CT2 PDBBind:  2AUZ IC50: 0.35 (nM) from 1 assay(s)
BindingDB:  2AUZ IC50: 0.35 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.193 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.704α = 90
b = 56.704β = 90
c = 130.375γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-08-08
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2018-02-14
    Changes: Experimental preparation
  • Version 1.5: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description