1TJC

Crystal structure of peptide-substrate-binding domain of human type I collagen prolyl 4-hydroxylase

1TJC の概要

• エントリーDOI: 10.2210/pdb1tjc/pdb
• 分子名称: Prolyl 4-hydroxylase alpha-1 subunit (2 entities in total)
• 機能のキーワード: tpr, helical bundle, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum lumen: P13674
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25466.49

構造登録者

Pekkala, M.,Hieta, R.,Bergmann, U.,Kivirikko, K.I.,Wierenga, R.K.,Myllyharju, J. (登録日: 2004-06-04, 公開日: 2004-10-12, 最終更新日: 2024-02-14)

主引用文献

Pekkala, M.,Hieta, R.,Bergmann, U.,Kivirikko, K.I.,Wierenga, R.K.,Myllyharju, J.
The Peptide-Substrate-binding Domain of Collagen Prolyl 4-Hydroxylases Is a Tetratricopeptide Repeat Domain with Functional Aromatic Residues.
J.Biol.Chem., 279:52255-52261, 2004

PubMed Abstract: Collagen prolyl 4-hydroxylases catalyze the formation of 4-hydroxyproline in -X-Pro-Gly-sequences and have an essential role in collagen synthesis. The vertebrate enzymes are alpha2beta2 tetramers in which the catalytic alpha-subunits contain separate peptide-substrate-binding and catalytic domains. We report on the crystal structure of the peptide-substrate-binding domain of the human type I enzyme refined at 2.3 A resolution. It was found to belong to a family of tetratricopeptide repeat domains that are involved in many protein-protein interactions and consist of five alpha-helices forming two tetratricopeptide repeat motifs plus the solvating helix. A prominent feature of its concave surface is a deep groove lined by tyrosines, a putative binding site for proline-rich Tripeptides. Solvent-exposed side chains of three of the tyrosines have a repeat distance similar to that of a poly-L-proline type II helix. The aromatic surface ends at one of the tyrosines, where the groove curves almost 90 degrees away from the linear arrangement of the three tyrosine side chains, possibly inducing a bent conformation in the bound peptide. This finding is consistent with previous suggestions by others that a minimal structural requirement for proline 4-hydroxylation may be a sequence in the poly-L-proline type II conformation followed by a beta-turn in the Pro-Gly segment. Site-directed mutagenesis indicated that none of the tyrosines was critical for tetramer assembly, whereas most of them were critical for the binding of a peptide substrate and inhibitor both to the domain and the alpha2beta2 enzyme tetramer.

PubMed: 15456751
DOI: 10.1074/jbc.M410007200

実験手法

X-RAY DIFFRACTION (2.3 Å)