2BDL | pdb_00002bdl

Cathepsin K complexed with a pyrrolidine ketoamide-based inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 
    0.241 (Depositor), 0.230 (DCC) 
  • R-Value Work: 
    0.193 (Depositor), 0.190 (DCC) 
  • R-Value Observed: 
    0.196 (Depositor) 

Starting Model: experimental
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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted 4PRClick on this verticalbar to view details

This is version 1.5 of the entry. See complete history. 


Literature

Novel, potent P2-P3 pyrrolidine derivatives of ketoamide-based cathepsin K inhibitors.

Barrett, D.G., Catalano, J.G., Deaton, D.N., Hassell, A.M., Long, S.T., Miller, A.B., Miller, L.R., Ray, J.A., Samano, V., Shewchuk, L.M., Wells-Knecht, K.J., Willard Jr., D.H., Wright, L.L.

(2006) Bioorg Med Chem Lett 16: 1735-1739

  • DOI: https://doi.org/10.1016/j.bmcl.2005.11.101
  • Primary Citation of Related Structures:  
    2BDL

  • PubMed Abstract: 

    Starting from a potent pantolactone ketoamide cathepsin K inhibitor discovered from structural screening, conversion of the lactone scaffold to a pyrrolidine scaffold allowed exploration of the S(3) subsite of cathepsin K. Manipulation of P3 and P1' groups afforded potent inhibitors with drug-like properties.

    • Organizational Affiliation: 

    Department of Medicinal Chemistry, 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: CTSK, CTSO, CTSO2
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
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
4PR
Query on 4PR
Download Ideal Coordinates CCD File 
B [auth A](3S)-1-{[(3,5-DIMETHYLISOXAZOL-4-YL)AMINO]CARBONYL}-4,4-DIMETHYLPYRROLIDIN-3-YL{(1S)-1-[1-HYDROXY-2-OXO-2-{[(1R)-1-PHENYLETHYL]AMINO}ETHYL]PENTYL}CARBAMATE
C28 H41 N5 O6
VVZICJQTDYOKIN-TYVKFHQSSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free:  0.241 (Depositor), 0.230 (DCC) 
  • R-Value Work:  0.193 (Depositor), 0.190 (DCC) 
  • R-Value Observed: 0.196 (Depositor) 
Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 38.06α = 90
b = 50.338β = 90
c = 105.891γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
SCALEPACKdata scaling
CNSrefinement
HKL-2000data collection
HKL-2000data reduction
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted 4PRClick on this verticalbar to view details

View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-03-21
    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: 2019-07-24
    Changes: Data collection, Derived calculations, Refinement description
  • Version 1.4: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.5: 2024-11-20
    Changes: Structure summary