1RWX

Crystal structure of human caspase-1 in complex with 4-oxo-3-{6-[4-(quinoxalin-2-yloxy)-benzoylamino]-2-thiophen-2-yl-hexanoylamino}-butyric acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.216 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Tethering identifies fragment that yields potent inhibitors of human caspase-1.

Fahr, B.T.O'Brien, T.Pham, P.Waal, N.D.Baskaran, S.Raimundo, B.C.Lam, J.W.Sopko, M.M.Purkey, H.E.Romanowski, M.J.

(2006) Bioorg Med Chem Lett 16: 559-562

  • DOI: https://doi.org/10.1016/j.bmcl.2005.10.048
  • Primary Citation of Related Structures:  
    1RWW, 1RWX

  • PubMed Abstract: 

    Disulfide Tethering was applied to the active site of human caspase-1, resulting in the discovery of a novel, tricyclic molecular fragment that selectively binds in S4. This fragment was developed into a class of potent inhibitors of human caspase-1. Several key analogues determined the optimal distance of the tricycle from the catalytic residues, the relative importance of various features of the tricycle, and the importance of the linker.


  • Organizational Affiliation

    Department of Chemistry, Sunesis Pharmaceuticals, 341 Oyster Point Boulevard, South San Francisco, CA 94080, USA. bfahr@sunesis.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Interleukin-1 beta convertase178Homo sapiensMutation(s): 0 
Gene Names: CASP1IL1BCIL1BCE
EC: 3.4.22.36
UniProt & NIH Common Fund Data Resources
Find proteins for P29466 (Homo sapiens)
Explore P29466 
Go to UniProtKB:  P29466
PHAROS:  P29466
GTEx:  ENSG00000137752 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP29466
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Interleukin-1 beta convertase88Homo sapiensMutation(s): 0 
Gene Names: CASP1IL1BCIL1BCE
EC: 3.4.22.36
UniProt & NIH Common Fund Data Resources
Find proteins for P29466 (Homo sapiens)
Explore P29466 
Go to UniProtKB:  P29466
PHAROS:  P29466
GTEx:  ENSG00000137752 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP29466
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
YBH
Query on YBH

Download Ideal Coordinates CCD File 
C [auth A]4-OXO-3-{6-[4-(QUINOXALIN-2-YLOXY)-BENZOYLAMINO]-2-THIOPHEN-2-YL-HEXANOYLAMINO}-BUTYRIC ACID
C29 H28 N4 O6 S
DJLHSAXTGGXZPX-UNMCSNQZSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
YBH PDBBind:  1RWX Ki: 43 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.216 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.371α = 90
b = 63.371β = 90
c = 162.399γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
CrystalCleardata reduction
d*TREKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-12-28
    Type: Initial release
  • Version 1.1: 2007-10-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description