2HBZ

Crystal structure of human caspase-1 (Arg286->Ala, Glu390->Ala) in complex with 3-[2-(2-benzyloxycarbonylamino-3-methyl-butyrylamino)-propionylamino]-4-oxo-pentanoic acid (z-VAD-FMK)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.225 

wwPDB Validation   3D Report Full Report


This is version 1.6 of the entry. See complete history


Literature

A Common Allosteric Site and Mechanism in Caspases

Scheer, J.M.Romanowski, M.J.Wells, J.A.

(2006) Proc Natl Acad Sci U S A 103: 7595-7600

  • DOI: https://doi.org/10.1073/pnas.0602571103
  • Primary Citation of Related Structures:  
    2FQQ, 2H48, 2HBQ, 2HBR, 2HBY, 2HBZ

  • PubMed Abstract: 

    We present a common allosteric mechanism for control of inflammatory and apoptotic caspases. Highly specific thiol-containing inhibitors of the human inflammatory caspase-1 were identified by using disulfide trapping, a method for site-directed small-molecule discovery. These compounds became trapped by forming a disulfide bond with a cysteine residue in the cavity at the dimer interface approximately 15 A away from the active site. Mutational and structural analysis uncovered a linear circuit of functional residues that runs from one active site through the allosteric cavity and into the second active site. Kinetic analysis revealed robust positive cooperativity not seen in other endopeptidases. Recently, disulfide trapping identified a similar small-molecule site and allosteric transition in the apoptotic caspase-7 that shares only a 23% sequence identity with caspase-1. Together, these studies show a general small-molecule-binding site for functionally reversing the zymogen activation of caspases and suggest a common regulatory site for the allosteric control of inflammation and apoptosis.


  • Organizational Affiliation

    Department of Pharmaceutical Chemistry, University of California, 1700 4th Street, San Francisco, CA 94143, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Caspase-1178Homo sapiensMutation(s): 1 
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
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Caspase-188Homo sapiensMutation(s): 1 
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:  Sequence   |   3D Structure  

Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
PHQ-VAD-fluoromethylketone inhibitor5N/AMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.225 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.245α = 90
b = 63.245β = 90
c = 142.241γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
d*TREKdata reduction
AMoREphasing
REFMACrefinement
CrystalCleardata reduction
d*TREKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-06-27
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Advisory, Atomic model, Database references, Derived calculations, Non-polymer description, Structure summary, Version format compliance
  • Version 1.3: 2012-05-30
    Changes: Database references
  • Version 1.4: 2012-12-12
    Changes: Other
  • Version 1.5: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.6: 2023-08-30
    Changes: Data collection, Refinement description