2FUN

alternative p35-caspase-8 complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.260 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Native chemical ligation in covalent caspase inhibition by p35.

Lu, M.Min, T.Eliezer, D.Wu, H.

(2006) Chem Biol 13: 117-122

  • DOI: https://doi.org/10.1016/j.chembiol.2005.12.007
  • Primary Citation of Related Structures:  
    2FUN

  • PubMed Abstract: 

    Wide-spectrum caspase inhibition by the baculoviral p35 protein was previously shown to be a consequence of covalent inhibition in which a thioester bond is stably formed between the cleavage residue Asp87 of p35 and the active site Cys360' of caspase-8. Here we show that the N-terminal fragment of cleaved p35 (p35-N) is a circular peptide when dissociated from the caspase. Biochemical and crystallographic data suggest that p35-N circularization results from the trapping of a native chemical ligation intermediate in the p35/caspase complex, in which the N-terminal Cys2 of p35 attacks the Asp87-Cys360' thioester to form an equilibrium between Asp87-Cys2 and Asp87-Cys360'. This provides a crucial covalent interaction for keeping the N terminus of p35 bound in the caspase active site, which explains the absolute requirement of Cys2 for caspase inhibition. Participation of native chemical ligation in caspase inhibition by p35 illustrates an unusual mechanism of protease inhibition.


  • Organizational Affiliation

    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Early 35 kDa protein
A, C
298Autographa californica nucleopolyhedrovirusMutation(s): 0 
Gene Names: P35
UniProt
Find proteins for P08160 (Autographa californica nuclear polyhedrosis virus)
Explore P08160 
Go to UniProtKB:  P08160
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08160
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
caspase-8
B, D
258Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q14790 (Homo sapiens)
Explore Q14790 
Go to UniProtKB:  Q14790
PHAROS:  Q14790
GTEx:  ENSG00000064012 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ14790
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.260 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 99.97α = 90
b = 117.34β = 90
c = 346.45γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
SOLVEphasing
CNSrefinement

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: Version format compliance
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Refinement description