3IO8

BimL12F in complex with Bcl-xL


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.187 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Conformational changes in Bcl-2 pro-survival proteins determine their capacity to bind ligands.

Lee, E.F.Czabotar, P.E.Yang, H.Sleebs, B.E.Lessene, G.Colman, P.M.Smith, B.J.Fairlie, W.D.

(2009) J Biol Chem 284: 30508-30517

  • DOI: https://doi.org/10.1074/jbc.M109.040725
  • Primary Citation of Related Structures:  
    3INQ, 3IO8, 3IO9

  • PubMed Abstract: 

    Antagonists of anti-apoptotic Bcl-2 family members hold promise as cancer therapeutics. Apoptosis is triggered when a peptide containing a BH3 motif or a small molecule BH3 peptidomimetic, such as ABT 737, binds to the relevant Bcl-2 family members. ABT-737 is an antagonist of Bcl-2, Bcl-x(L), and Bcl-w but not of Mcl-1. Here we describe new structures of mutant BH3 peptides bound to Bcl-x(L) and Mcl-1. These structures suggested a rationale for the failure of ABT-737 to bind Mcl-1, but a designed variant of ABT-737 failed to acquire binding affinity for Mcl-1. Rather, it was selective for Bcl-x(L), a result attributable in part to significant backbone refolding and movements of helical segments in its ligand binding site. To date there are few reported crystal structures of organic ligands in complex with their pro-survival protein targets. Our structure of this new organic ligand provided insights into the structural transitions that occur within the BH3 binding groove, highlighting significant differences in the structural properties of members of the Bcl-2 pro-survival protein family. Such differences are likely to influence and be important in the quest for compounds capable of selectively antagonizing the different family members.


  • Organizational Affiliation

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Bcl-2-like protein 1
A, C
158Homo sapiensMutation(s): 0 
Gene Names: BCL2L1BCL2LBCLX
UniProt & NIH Common Fund Data Resources
Find proteins for Q07817 (Homo sapiens)
Explore Q07817 
Go to UniProtKB:  Q07817
PHAROS:  Q07817
GTEx:  ENSG00000171552 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ07817
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Bcl-2-like protein 11
B, D
26Homo sapiensMutation(s): 1 
UniProt & NIH Common Fund Data Resources
Find proteins for O43521 (Homo sapiens)
Explore O43521 
Go to UniProtKB:  O43521
PHAROS:  O43521
GTEx:  ENSG00000153094 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO43521
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.187 
  • Space Group: P 62
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.717α = 90
b = 65.717β = 90
c = 170.094γ = 120
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
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: 2009-09-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-07-26
    Changes: Advisory, Data collection, Refinement description, Source and taxonomy
  • Version 1.3: 2021-10-13
    Changes: Advisory, Database references, Derived calculations
  • Version 1.4: 2023-09-06
    Changes: Data collection, Refinement description