6FXK

Crystal Structure of full-length Human Lysyl Hydroxylase LH3

6FXK の概要

• エントリーDOI: 10.2210/pdb6fxk/pdb
• 分子名称: Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: lysyl hydroxylase, galacosyltransferase, glucosyltransferase, collagen, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 83816.15

構造登録者

Scietti, L.,Chiapparino, A.,De Giorgi, F.,Fumagalli, M.,Khoriauli, L.,Nergadze, S.,Basu, S.,Olieric, V.,Banushi, B.,Giulotto, E.,Gissen, P.,Forneris, F. (登録日: 2018-03-09, 公開日: 2018-08-22, 最終更新日: 2024-10-09)

主引用文献

Scietti, L.,Chiapparino, A.,De Giorgi, F.,Fumagalli, M.,Khoriauli, L.,Nergadze, S.,Basu, S.,Olieric, V.,Cucca, L.,Banushi, B.,Profumo, A.,Giulotto, E.,Gissen, P.,Forneris, F.
Molecular architecture of the multifunctional collagen lysyl hydroxylase and glycosyltransferase LH3.
Nat Commun, 9:3163-3163, 2018

PubMed Abstract: Lysyl hydroxylases catalyze hydroxylation of collagen lysines, and sustain essential roles in extracellular matrix (ECM) maturation and remodeling. Malfunctions in these enzymes cause severe connective tissue disorders. Human lysyl hydroxylase 3 (LH3/PLOD3) bears multiple enzymatic activities, as it catalyzes collagen lysine hydroxylation and also their subsequent glycosylation. Our understanding of LH3 functions is currently hampered by lack of molecular structure information. Here, we present high resolution crystal structures of full-length human LH3 in complex with cofactors and donor substrates. The elongated homodimeric LH3 architecture shows two distinct catalytic sites at the N- and C-terminal boundaries of each monomer, separated by an accessory domain. The glycosyltransferase domain displays distinguishing features compared to other known glycosyltransferases. Known disease-related mutations map in close proximity to the catalytic sites. Collectively, our results provide a structural framework characterizing the multiple functions of LH3, and the molecular mechanisms of collagen-related diseases involving human lysyl hydroxylases.

PubMed: 30089812
DOI: 10.1038/s41467-018-05631-5

実験手法

X-RAY DIFFRACTION (2.7 Å)