9BB5

Backbone Modification in the GA Module of Protein PAB: ACPC residues at positions 22 and 26

Summary for 9BB5

• Entry DOI: 10.2210/pdb9bb5/pdb
• NMR Information: BMRB: 31161
• Descriptor: Peptostreptococcal albumin-binding protein (1 entity in total)
• Functional Keywords: helix bundle, designed variant, protein binding
• Biological source: Finegoldia magna
• Total number of polymer chains: 1
• Total formula weight: 5126.90

Authors

Lin, Y.,Horne, W.S. (deposition date: 2024-04-05, release date: 2024-06-05, Last modification date: 2024-08-21)

Primary citation

Lin, Y.,Horne, W.S.
Backbone Modification in a Protein Hydrophobic Core.
Chemistry, 30:e202401890-e202401890, 2024

PubMed Abstract: Targeted protein backbone modification can recreate tertiary structures reminiscent of folds found in nature on artificial scaffolds with improved biostability. Incorporation of altered monomers in such entities is typically limited to sites distant from the hydrophobic core to avoid potential disruptions to folding. This is limiting, as it is advantageous in some applications to incorporate artificial connectivity at buried sites. Here, we report an examination of protein backbone modification targeted specifically to hydrophobic core positions and its impacts on tertiary folded structure and fold stability. Different artificial monomer types are placed at core, core-flanking, or solvent-exposed positions in a compact three-helix protein. Effects on structure and folding energetics are assessed by NMR spectroscopy and biophysical methods. Results show that artificial residues can be well accommodated in the hydrophobic core of a defined tertiary fold, with effects on stability only modestly larger than identical changes at solvent-exposed sites. Collectively, these results provide new insights into folding behavior of protein-like artificial chains as well as strategies for the design of such molecules.

PubMed: 38753977
DOI: 10.1002/chem.202401890

Experimental method

SOLUTION NMR