Decoding elegant interplay among different stereo-electronic effects due to the ancient prolyl-4-hydroxylation stabilizing collagenous helicity.

ABSTRACT: Prolyl-4-hydroxylation is an ancient evolutionarily conserved post-translational modification (PTM) critical for both structural and regulatory functions in multicellular life forms. This PTM plays a pivotal role in stabilizing collagen's triple helix by influencing the puckering of the pyrrolidine ring. The elegant interplay between ring pucker, torsional angles, peptide bond isomerization, and charge-transfer interactions (O···C=O n→π∗ and σ→σ∗) attaining the helical stability remains underappreciated. Using density functional theory calibrated against gold standard ab initio methods, we analyzed a physiologically relevant collagenous peptide proline-4-hydroxyproline-glycine (PO⁴G) to establish the correlation between stereo-electronic effects due to prolyl-4-hydroxylat

SUBMITTER: Joshi A 

PROVIDER: S-EPMC12059709 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature