Stabilization of the Collagen Triple Helix by O-Methylation of Hydroxyproline Residues

摘要

The hydroxylation of proline residues in collagen is the most common posttranslational modification in humans. The hydroxylation is stereoselective, affording (2S,4R)-4-hydroxyproline (Hyp) in the Yaa position of the canonical Xaa-Yaa-Gly triad and thereby bestowing marked stabilization upon the collagen triple helix. The means by which Hyp stabilizes collagen has engendered dispute. One hypothesis suggests that a network of water molecules links the Hyp hydroxyl groups and main-chain carbonyl groups. An alternative hypothesis invokes a stereoelectronic effect by which the electronegative oxygen preorganizes the main chain in the proper conformation for triple-helix formation.