4HU5

Oxime side-chain cross-links in the GCN4-p1 dimeric coiled coil: Linear precursor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.268 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Oxime Side-Chain Cross-Links in an alpha-Helical Coiled-Coil Protein: Structure, Thermodynamics, and Folding-Templated Synthesis of Bicyclic Species.

Haney, C.M.Horne, W.S.

(2013) Chemistry 19: 11342-11351

  • DOI: https://doi.org/10.1002/chem.201300506
  • Primary Citation of Related Structures:  
    4HU5, 4HU6

  • PubMed Abstract: 

    Covalent side-chain cross-links are a versatile method to control peptide folding, particularly when α-helical secondary structure is the target. Here, we examine the application of oxime bridges, formed by the chemoselective reaction between aminooxy and aldehyde side chains, for the stabilization of a helical peptide involved in a protein-protein complex. A series of sequence variants of the dimeric coiled coil GCN4-p1 bearing oxime bridges at solvent-exposed positions were prepared and biophysically characterized. Triggered unmasking of a side-chain aldehyde in situ and subsequent cyclization proceed rapidly and cleanly at pH 7 in the folded protein complex. Comparison of folding thermodynamics among a series of different oxime bridges show that the cross links are consistently stabilizing to the coiled coil, with the extent of stabilization sensitive to the exact size and structure of the macrocycle. X-ray crystallographic analysis of a coiled coil with the best cross link in place and a second structure of its linear precursor show how the bridge is accommodated into an α-helix. Preparation of a bicyclic oligomer by simultaneous formation of two linkages in situ demonstrates the potential use of triggered oxime formation to both trap and stabilize a particular peptide folded conformation in the bound state.


  • Organizational Affiliation

    Department of Chemistry, University of Pittsburgh, 219 Parkman Ave., Pittsburgh, PA 15260, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
General control protein GCN4
A, B
35Saccharomyces cerevisiae S288CMutation(s): 3 
UniProt
Find proteins for P03069 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
Explore P03069 
Go to UniProtKB:  P03069
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03069
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.268 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.206 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 76.729α = 90
b = 30.907β = 97.75
c = 33.306γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-08-21
    Type: Initial release
  • Version 1.1: 2013-09-11
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 2.0: 2023-11-15
    Changes: Advisory, Atomic model, Data collection