3HEX

Cyclic residues in alpha/beta-peptide helix bundles: GCN4-pLI side chain sequence on an (alpha-alpha-beta) backbone with cyclic beta-residues at positions 1, 4, 19 and 28


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.298 
  • R-Value Work: 0.272 
  • R-Value Observed: 0.273 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Structural consequences of beta-amino acid preorganization in a self-assembling alpha/beta-peptide: fundamental studies of foldameric helix bundles.

Price, J.L.Horne, W.S.Gellman, S.H.

(2010) J Am Chem Soc 132: 12378-12387

  • DOI: https://doi.org/10.1021/ja103543s
  • Primary Citation of Related Structures:  
    3HET, 3HEU, 3HEV, 3HEW, 3HEX, 3HEY

  • PubMed Abstract: 

    We report high-resolution crystal structures of six new alpha/beta-peptide foldamers that have a regular alpha-residue/alpha-residue/beta-residue (alphaalphabeta) backbone repeat pattern. All of these foldamers were crystallized from aqueous solution, and all display four-helix bundle quaternary structure in the crystalline state. These oligomers are based on the well-studied 33-residue alpha-peptide GCN4-pLI, which is an engineered derivative of the dimerization domain of GCN4, a yeast transcription factor. GCN4-pLI forms a stable tetramer in solution and crystallizes as a four-helix bundle (Harbury et al. Science 1993, 262, 1401-1407). Previously we described a foldamer (designated 1 here) that was generated from GCN4-pLI by replacing every third alpha-amino acid residue with the homologous beta(3)-amino acid residue; this alphaalphabeta oligomer retains the side chain sequence of the original alpha-peptide, but the backbone contains 11 additional CH(2) units, which are evenly distributed (Horne et al. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 9151-9156). Despite the expanded backbone, 1 was found to retain the ability to form a tetrameric quaternary structure in which the individual molecules adopt an alpha-helix-like conformation. Here we compare nine analogues of 1 that have the same alphaalphabeta backbone but in which one or more of the flexible beta(3)-amino acid residues is/are replaced with an analogous cyclic beta-residue. The motivation for beta(3)-->cyclic replacements is to enhance conformational stability; however, a crystal structure of the one previously reported example (designated 2 here) revealed a "stammer" distortion of the helix-bundle architecture relative to 1. The results reported here suggest that the stammer is a peculiarity of 2, because all six of the new alpha/beta-peptides display undistorted four-helix bundle quaternary structures. More broadly, our results indicate that beta(3)-->cyclic replacements are generally well-accommodated in helix-bundle quaternary structure, but that such replacements can be destabilizing in certain instances.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
alpha/beta-peptide based on the GCN4-pLI side chain sequence with an (alpha-alpha-beta) backbone and cyclic beta-residues at positions 1, 4, 19 and 2834N/AMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  3 Unique
IDChains TypeFormula2D DiagramParent
B3D
Query on B3D
A
PEPTIDE-LIKEC5 H9 N O4ASP
B3E
Query on B3E
A
L-PEPTIDE LINKINGC6 H11 N O4GLU
HMR
Query on HMR
A
L-PEPTIDE LINKINGC7 H16 N4 O2ARG
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.298 
  • R-Value Work: 0.272 
  • R-Value Observed: 0.273 
  • Space Group: P 4 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 38.124α = 90
b = 38.124β = 90
c = 46.126γ = 90
Software Package:
Software NamePurpose
PROTEUM PLUSdata collection
PHASERphasing
REFMACrefinement
PROTEUM PLUSdata reduction
PROTEUM PLUSdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-04-21
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 2.0: 2023-11-15
    Changes: Atomic model, Data collection