5GZ8

Crystal structure of catalytic domain of Protein O-mannosyl Kinase in ligand-free form

5GZ8 の概要

• エントリーDOI: 10.2210/pdb5gz8/pdb
• 関連するPDBエントリー: 5GZ9
• 分子名称: Protein O-mannose kinase (2 entities in total)
• 機能のキーワード: sugar kinase, dystroglycanopathy, o-mannosylation, transferase
• 由来する生物種: Mus musculus (Mouse)
• 細胞内の位置: Endoplasmic reticulum membrane ; Single-pass type II membrane protein : Q3TUA9
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35213.11

構造登録者

Nagae, M.,Yamaguchi, Y. (登録日: 2016-09-27, 公開日: 2017-03-29, 最終更新日: 2024-10-16)

主引用文献

Nagae, M.,Mishra, S.K.,Neyazaki, M.,Oi, R.,Ikeda, A.,Matsugaki, N.,Akashi, S.,Manya, H.,Mizuno, M.,Yagi, H.,Kato, K.,Senda, T.,Endo, T.,Nogi, T.,Yamaguchi, Y.
3D structural analysis of protein O-mannosyl kinase, POMK, a causative gene product of dystroglycanopathy.
Genes Cells, 22:348-359, 2017

PubMed Abstract: Orchestration of the multiple enzymes engaged in O-mannose glycan synthesis provides a matriglycan on α-dystroglycan (α-DG) which attracts extracellular matrix (ECM) proteins such as laminin. Aberrant O-mannosylation of α-DG leads to severe congenital muscular dystrophies due to detachment of ECM proteins from the basal membrane. Phosphorylation at C6-position of O-mannose catalyzed by protein O-mannosyl kinase (POMK) is a crucial step in the biosynthetic pathway of O-mannose glycan. Several mis-sense mutations of the POMK catalytic domain are known to cause a severe congenital muscular dystrophy, Walker-Warburg syndrome. Due to the low sequence similarity with other typical kinases, structure-activity relationships of this enzyme remain unclear. Here, we report the crystal structures of the POMK catalytic domain in the absence and presence of an ATP analogue and O-mannosylated glycopeptide. The POMK catalytic domain shows a typical protein kinase fold consisting of N- and C-lobes. Mannose residue binds to POMK mainly via the hydroxyl group at C2-position, differentiating from other monosaccharide residues. Intriguingly, the two amino acid residues K92 and D228, interacting with the triphosphate group of ATP, are donated from atypical positions in the primary structure. Mutations in this protein causing muscular dystrophies can now be rationalized.

PubMed: 28251761
DOI: 10.1111/gtc.12480

実験手法

X-RAY DIFFRACTION (2.5 Å)