4ZEL

Human dopamine beta-hydroxylase

4ZEL の概要

• エントリーDOI: 10.2210/pdb4zel/pdb
• 分子名称: Dopamine beta-hydroxylase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: hydroxylase, dimer, copper binding, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Soluble dopamine beta-hydroxylase: Cytoplasmic vesicle, secretory vesicle lumen. Cytoplasmic vesicle, secretory vesicle membrane; Single-pass type II membrane protein: P09172
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 132883.70

構造登録者

Vendelboe, T.V.,Harris, P.,Christensen, H.E.M.,Harlos, K.,Walter, T.,Zhao, Y.,Omari, K. (登録日: 2015-04-20, 公開日: 2016-04-20, 最終更新日: 2024-10-09)

主引用文献

Vendelboe, T.V.,Harris, P.,Zhao, Y.,Walter, T.S.,Harlos, K.,El Omari, K.,Christensen, H.E.
The crystal structure of human dopamine beta-hydroxylase at 2.9 angstrom resolution.
Sci Adv, 2:e1500980-e1500980, 2016

PubMed Abstract: The norepinephrine pathway is believed to modulate behavioral and physiological processes, such as mood, overall arousal, and attention. Furthermore, abnormalities in the pathway have been linked to numerous diseases, for example hypertension, depression, anxiety, Parkinson's disease, schizophrenia, Alzheimer's disease, attention deficit hyperactivity disorder, and cocaine dependence. We report the crystal structure of human dopamine β-hydroxylase, which is the enzyme converting dopamine to norepinephrine. The structure of the DOMON (dopamine β-monooxygenase N-terminal) domain, also found in >1600 other proteins, reveals a possible metal-binding site and a ligand-binding pocket. The catalytic core structure shows two different conformations: an open active site, as also seen in another member of this enzyme family [the peptidylglycine α-hydroxylating (and α-amidating) monooxygenase], and a closed active site structure, in which the two copper-binding sites are only 4 to 5 Å apart, in what might be a coupled binuclear copper site. The dimerization domain adopts a conformation that bears no resemblance to any other known protein structure. The structure provides new molecular insights into the numerous devastating disorders of both physiological and neurological origins associated with the dopamine system.

PubMed: 27152332
DOI: 10.1126/sciadv.1500980

実験手法

X-RAY DIFFRACTION (2.9 Å)