4JJE

Caspase-3 specific unnatural amino acid peptides


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.48 Å
  • R-Value Free: 0.174 
  • R-Value Work: 0.150 
  • R-Value Observed: 0.151 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Selective Detection of Caspase-3 versus Caspase-7 Using Activity-Based Probes with Key Unnatural Amino Acids.

Vickers, C.J.Gonzalez-Paez, G.E.Wolan, D.W.

(2013) ACS Chem Biol 8: 1558-1566

  • DOI: https://doi.org/10.1021/cb400209w
  • Primary Citation of Related Structures:  
    4JJ7, 4JJ8, 4JJE

  • PubMed Abstract: 

    Caspases are required for essential biological functions, most notably apoptosis and pyroptosis, but also cytokine production, cell proliferation, and differentiation. One of the most well studied members of this cysteine protease family includes executioner caspase-3, which plays a central role in cell apoptosis and differentiation. Unfortunately, there exists a dearth of chemical tools to selectively monitor caspase-3 activity under complex cellular and in vivo conditions due to its close homology with executioner caspase-7. Commercially available activity-based probes and substrates rely on the canonical DEVD tetrapeptide sequence, which both caspases-3 and -7 recognize with similar affinity, and thus the individual contributions of caspase-3 and/or -7 toward important cellular processes are irresolvable. Here, we analyzed a variety of permutations of the DEVD peptide sequence in order to discover peptides with biased activity and recognition of caspase-3 versus caspases-6, -7, -8, and -9. Through this study, we identify fluorescent and biotinylated probes capable of selective detection of caspase-3 using key unnatural amino acids. Likewise, we determined the X-ray crystal structures of caspases-3, -7, and -8 in complex with our lead peptide inhibitor to elucidate the binding mechanism and active site interactions that promote the selective recognition of caspase-3 over other highly homologous caspase family members.


  • Organizational Affiliation

    Departments of Molecular and Experimental Medicine and Chemical Physiology, The Scripps Research Institute , La Jolla, California 92037, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Caspase-3257Homo sapiensMutation(s): 0 
Gene Names: CASP3Caspase-3 CPP32CPP32
EC: 3.4.22.56
UniProt & NIH Common Fund Data Resources
Find proteins for P42574 (Homo sapiens)
Explore P42574 
Go to UniProtKB:  P42574
PHAROS:  P42574
GTEx:  ENSG00000164305 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP42574
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Caspase inhibitor6N/AMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.48 Å
  • R-Value Free: 0.174 
  • R-Value Work: 0.150 
  • R-Value Observed: 0.151 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.11α = 90
b = 84.334β = 90
c = 96.088γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SOLVEphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-06-12
    Type: Initial release
  • Version 1.1: 2014-02-19
    Changes: Database references
  • Version 2.0: 2023-11-15
    Changes: Atomic model, Data collection, Database references, Derived calculations