Structural studies on peptide binding domain of human type I collagen prolyl 4-hydroxylase

Collagen prolyl 4-hydroxylase (C-P4H) catalyses the formation of 4-hydroxyproline in collagens. Hydroxylation of prolines in –X-Pro-Glysequences is necessary for the formation of stable collagen triple helices. Molecular oxygen, Fe, 2-oxogluterate and ascorbate are required for the reaction [1]. In vertebrates C-P4H is an 2 2 tetramer in which is the catalytic subunit and the subunit is identical to the protein disulfide isomerase (PDI). Proline-rich-peptide binding domain of the subunit is separate from the catalytic domain and is located between residues Gly138 and Ser244 [2]. In fibrotic diseases inhibition of excessive collagen synthesis can be attained by inhibiting C-P4Hs. Development of inhibitors would benefit from stuctural information of C-P4Hs. Crystallisation of full length human C-P4H has not been succesful so far but attempts to crystallise a peptide binding domain of it has produced diffracting crystals.