PDBsum entry 6e5h

De novo protein

PDB id: 6e5h

Contents

Protein chain

28 a.a.

PDB id:

6e5h

Name:

De novo protein

Title:

Heterogeneous-backbone mimics of a designed disulfide-rich protein: aib turn

Structure:

Designed peptide nc_hee_d1: aib turn mutant. Chain: a. Engineered: yes

Source:

Synthetic: yes. Synthetic construct. Organism_taxid: 32630

NMR struc:

10 models

Authors:

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

Key ref:

C.C.Cabalteja et al. (2019). Heterogeneous-Backbone Foldamer Mimics of a Computationally Designed, Disulfide-Rich Miniprotein. Chembiochem, 20, 103-110. PubMed id: 30326175 DOI: 10.1002/cbic.201800558

Date:

20-Jul-18 Release date: 21-Nov-18

Protein chain

No UniProt id for this chain

Struc: 28 a.a.

DOI no: 10.1002/cbic.201800558

Chembiochem 20:103-110 (2019)

PubMed id: 30326175

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

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

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.