EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation.
ジャーナル・号・ページ	Nat Commun, Vol. 13, Issue 1, Page 74, Year 2022
掲載日	2022年1月10日
著者	María Teresa Bueno-Carrasco / Jorge Cuéllar / Marte I Flydal / César Santiago / Trond-André Kråkenes / Rune Kleppe / José R López-Blanco / Miguel Marcilla / Knut Teigen / Sara Alvira / Pablo Chacón / Aurora Martinez / José M Valpuesta /
PubMed 要旨	Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of dopamine (DA) and other catecholamines, and its dysfunction leads to DA deficiency and parkinsonisms. Inhibition by ...Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of dopamine (DA) and other catecholamines, and its dysfunction leads to DA deficiency and parkinsonisms. Inhibition by catecholamines and reactivation by S40 phosphorylation are key regulatory mechanisms of TH activity and conformational stability. We used Cryo-EM to determine the structures of full-length human TH without and with DA, and the structure of S40 phosphorylated TH, complemented with biophysical and biochemical characterizations and molecular dynamics simulations. TH presents a tetrameric structure with dimerized regulatory domains that are separated 15 Å from the catalytic domains. Upon DA binding, a 20-residue α-helix in the flexible N-terminal tail of the regulatory domain is fixed in the active site, blocking it, while S40-phosphorylation forces its egress. The structures reveal the molecular basis of the inhibitory and stabilizing effects of DA and its counteraction by S40-phosphorylation, key regulatory mechanisms for homeostasis of DA and TH.
リンク	Nat Commun / PubMed:35013193 / PubMed Central
手法	EM (単粒子)
解像度	3.5 - 4.6 Å
構造データ	11309 6zn2 EMDB-11309, PDB-6zn2: Partial structure of tyrosine hydroxylase in complex with dopamine showing the catalytic domain and an alpha-helix from the regulatory domain involved in dopamine binding. 手法: EM (単粒子) / 解像度: 4.3 Å 11467 6zvp EMDB-11467, PDB-6zvp: Atomic model of the EM-based structure of the full-length tyrosine hydroxylase in complex with dopamine (residues 40-497) in which the regulatory domain (residues 40-165) has been included only with the backbone atoms 手法: EM (単粒子) / 解像度: 4.0 Å 11587 6zzu EMDB-11587, PDB-6zzu: Partial structure of the substrate-free tyrosine hydroxylase (apo-TH). 手法: EM (単粒子) / 解像度: 3.5 Å 11624 7a2g EMDB-11624, PDB-7a2g: Full-length structure of the substrate-free tyrosine hydroxylase (apo-TH). 手法: EM (単粒子) / 解像度: 4.1 Å EMDB-13177: Ser40 phosphorylated tyrosine hydroxylase 手法: EM (単粒子) / 解像度: 4.5 Å 13442 7pim EMDB-13442, PDB-7pim: Partial structure of tyrosine hydroxylase lacking the first 35 residues in complex with dopamine. 手法: EM (単粒子) / 解像度: 4.6 Å
化合物	ChemComp-LDP: L-DOPAMINE / ド-パミン / 薬剤YM / Dopamine (medication) ChemComp-FE: Unknown entry / 鉄 ChemComp-HOH*: WATER / 水
由来	homo sapiens (ヒト)
キーワード	OXIDOREDUCTASE (酸化還元酵素) / Tetramer (四量体) / Dopamine (ドーパミン) / Catecholamine (カテコールアミン) / Brain (脳) / Parkinson (パーキンソン病)