6E5H

Heterogeneous-Backbone Mimics of a Designed Disulfide-Rich Protein: Aib turn


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Heterogeneous-Backbone Foldamer Mimics of a Computationally Designed, Disulfide-Rich Miniprotein.

Cabalteja, C.C.Mihalko, D.S.Horne, W.S.

(2019) Chembiochem 20: 103-110

  • DOI: https://doi.org/10.1002/cbic.201800558
  • Primary Citation of Related Structures:  
    6E5H, 6E5I, 6E5J, 6E5K

  • PubMed Abstract: 

    Disulfide-rich peptides have found widespread use in the development of bioactive agents; however, low proteolytic stability and the difficulty of exerting synthetic control over chain topology present barriers to their application in some systems. Herein, we report a method that enables the creation of artificial backbone ("foldamer") mimics of compact, disulfide-rich tertiary folds. Systematic replacement of a subset of natural α-residues with various artificial building blocks in the context of a computationally designed prototype sequence leads to "heterogeneous-backbone" variants that undergo clean oxidative folding, adopt tertiary structures indistinguishable from that of the prototype, and enjoy proteolytic protection beyond that inherent to the topologically constrained scaffold. Collectively, these results demonstrate systematic backbone substitution to be a viable method to engineer the properties of disulfide-rich sequences and expands the repertoire of protein mimicry by foldamers to an exciting new structural class.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Designed peptide NC_HEE_D1: Aib turn mutant28synthetic constructMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
AIB
Query on AIB
A
L-PEPTIDE LINKINGC4 H9 N O2ALA
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United States107161

Revision History  (Full details and data files)

  • Version 1.0: 2018-11-21
    Type: Initial release
  • Version 1.1: 2019-01-16
    Changes: Data collection, Database references
  • Version 1.2: 2020-01-01
    Changes: Author supporting evidence, Data collection
  • Version 1.3: 2023-06-14
    Changes: Database references, Other