2009/12/31 by Matthew D. Shoulders, Kenneth A. Satyshur, Katrina T. Forest +1 · 1 citation
Materials Science · Biochemistry, Genetics and Molecular Biology · #Enzyme Structure and Function #Protein Structure and Dynamics #Collagen: Extraction and Characterization
paper · doi:10.1073/pnas.0909592107
openalex publication_date 2009/12/31 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Preorganization is shown to endow a protein with extraordinary conformational stability. This preorganization is achieved by installing side-chain substituents that impose stereoelectronic and steric effects that restrict main-chain torsion angles. Replacing proline residues in (ProProGly)(7) collagen strands with 4-fluoroproline and 4-methylproline leads to the most stable known triple helices, having T ( m ) values that are increased by > 50 degrees C. Differential scanning calorimetry data indicate an entropic basis to the hyperstability, as expected from an origin in preorganization. Structural data at a resolution of 1.21 A reveal a prototypical triple helix with insignificant deviations to its main chain, even though 2/3 of the residues are nonnatural. Thus, preorganization of a main chain by subtle changes to side chains can confer extraordinary conformational stability upon a protein without perturbing its structure.