4A1W

Crystal structure of alpha-beta foldamer 4c in complex with Bcl-xL


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.200 

wwPDB Validation   3D Report Full Report


This is version 3.1 of the entry. See complete history


Literature

Evaluation of Diverse Alpha/Beta-Backbone Patterns for Functional Alpha-Helix Mimicry: Analogues of the Bim Bh3 Domain.

Boersma, M.D.Haase, H.S.Peterson-Kaufman, K.J.Lee, E.F.Clarke, O.B.Colman, P.M.Smith, B.J.Horne, W.S.Fairlie, W.D.Gellman, S.H.

(2012) J Am Chem Soc 134: 315

  • DOI: https://doi.org/10.1021/ja207148m
  • Primary Citation of Related Structures:  
    4A1U, 4A1W

  • PubMed Abstract: 

    Peptidic oligomers that contain both α- and β-amino acid residues, in regular patterns throughout the backbone, are emerging as structural mimics of α-helix-forming conventional peptides (composed exclusively of α-amino acid residues). Here we describe a comprehensive evaluation of diverse α/β-peptide homologues of the Bim BH3 domain in terms of their ability to bind to the BH3-recognition sites on two partner proteins, Bcl-x(L) and Mcl-1. These proteins are members of the anti-apoptotic Bcl-2 family, and both bind tightly to the Bim BH3 domain itself. All α/β-peptide homologues retain the side-chain sequence of the Bim BH3 domain, but each homologue contains periodic α-residue → β(3)-residue substitutions. Previous work has shown that the ααβαααβ pattern, which aligns the β(3)-residues in a 'stripe' along one side of the helix, can support functional α-helix mimicry, and the results reported here strengthen this conclusion. The present study provides the first evaluation of functional mimicry by ααβ and αααβ patterns, which cause the β(3)-residues to spiral around the helix periphery. We find that the αααβ pattern can support effective mimicry of the Bim BH3 domain, as manifested by the crystal structure of an α/β-peptide bound to Bcl-x(L), affinity for a variety of Bcl-2 family proteins, and induction of apoptotic signaling in mouse embryonic fibroblast extracts. The best αααβ homologue shows substantial protection from proteolytic degradation relative to the Bim BH3 α-peptide.


  • Organizational Affiliation

    Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BCL-2-LIKE PROTEIN 1
A, B, C, D
158Homo sapiensMutation(s): 0 
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
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
ALPHA-BETA-FOLDAMER 2CE [auth P],
F [auth Q],
G [auth R],
H [auth S]
19synthetic constructMutation(s): 0 
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
Small Molecules
Modified Residues  3 Unique
IDChains TypeFormula2D DiagramParent
B3E
Query on B3E
E [auth P],
F [auth Q],
G [auth R],
H [auth S]
L-PEPTIDE LINKINGC6 H11 N O4GLU
B3Y
Query on B3Y
E [auth P],
F [auth Q],
G [auth R],
H [auth S]
L-PEPTIDE LINKINGC10 H13 N O3TYR
HT7
Query on HT7
E [auth P],
F [auth Q],
G [auth R],
H [auth S]
L-PEPTIDE LINKINGC12 H14 N2 O2TRP
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.200 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.213α = 90
b = 106.29β = 90
c = 100.44γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
SCALEPACKdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-12-28
    Type: Initial release
  • Version 1.1: 2012-01-25
    Changes: Other
  • Version 1.2: 2012-11-30
    Changes: Other
  • Version 1.3: 2018-06-20
    Changes: Advisory, Data collection, Derived calculations
  • Version 2.0: 2019-04-24
    Changes: Data collection, Polymer sequence
  • Version 2.1: 2019-07-10
    Changes: Data collection
  • Version 3.0: 2023-11-15
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Other
  • Version 3.1: 2023-12-20
    Changes: Refinement description