8ES3

Backbone modifications in the inter-helix loop of designed miniprotein oPPalpha: DPro10Pro11 turn

Summary for 8ES3

• Entry DOI: 10.2210/pdb8es3/pdb
• NMR Information: BMRB: 31053
• Descriptor: Designed miniprotein oPPalpha: DPro10Pro11 turn (1 entity in total)
• Functional Keywords: protein mimetic, heterogeneous backbone, de novo protein
• Biological source: Streptococcus mutans
• Total number of polymer chains: 1
• Total formula weight: 3756.39

Authors

Harmon, T.W.,Horne, W.S. (deposition date: 2022-10-13, release date: 2023-04-05, Last modification date: 2024-10-30)

Primary citation

Harmon, T.W.,Horne, W.S.
Protein Backbone Alteration in Non-Hairpin beta-Turns: Impacts on Tertiary Folded Structure and Folded Stability.
Chembiochem, 24:e202300113-e202300113, 2023

PubMed Abstract: The importance of β-turns to protein folding has motivated extensive efforts to stabilize the motif with non-canonical backbone connectivity. Prior work has focused almost exclusively on turns between strands in a β-sheet (i. e., hairpins). Turns in other structural contexts are also common in nature and have distinct conformational preferences; however, design principles for their mimicry remain poorly understood. Here, we report strategies that stabilize non-hairpin β-turns through systematic evaluation of the impacts of backbone alteration on the high-resolution folded structure and folded stability of a helix-loop-helix prototype protein. Several well-established hairpin turn mimetics are shown detrimental to folded stability and/or hydrophobic core packing, while less-explored modification schemes that reinforce alternate turn types lead to improved stability and more faithful structural mimicry. Collectively, these results have implications in control over protein folding through chemical modification as well as the design of protein mimetics.

PubMed: 36920327
DOI: 10.1002/cbic.202300113

Experimental method

SOLUTION NMR