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基本情報
登録情報 | データベース: PDB / ID: 7pim | |||||||||
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タイトル | Partial structure of tyrosine hydroxylase lacking the first 35 residues in complex with dopamine. | |||||||||
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![]() | OXIDOREDUCTASE / Tetramer / Dopamine / Catecholamine / Brain / Parkinson | |||||||||
機能・相同性 | ![]() tyrosine 3-monooxygenase / tyrosine 3-monooxygenase activity / phytoalexin metabolic process / dopamine biosynthetic process from tyrosine / phthalate metabolic process / glycoside metabolic process / terpene metabolic process / isoquinoline alkaloid metabolic process / norepinephrine biosynthetic process / embryonic camera-type eye morphogenesis ...tyrosine 3-monooxygenase / tyrosine 3-monooxygenase activity / phytoalexin metabolic process / dopamine biosynthetic process from tyrosine / phthalate metabolic process / glycoside metabolic process / terpene metabolic process / isoquinoline alkaloid metabolic process / norepinephrine biosynthetic process / embryonic camera-type eye morphogenesis / hyaloid vascular plexus regression / epinephrine biosynthetic process / circadian sleep/wake cycle / Catecholamine biosynthesis / aminergic neurotransmitter loading into synaptic vesicle / response to pyrethroid / dopamine binding / eye photoreceptor cell development / response to isolation stress / sphingolipid metabolic process / melanosome membrane / response to ether / synaptic transmission, dopaminergic / tetrahydrobiopterin binding / response to herbicide / mating behavior / dopamine biosynthetic process / amino acid binding / regulation of heart contraction / eating behavior / response to corticosterone / pigmentation / response to zinc ion / cellular response to alkaloid / social behavior / response to immobilization stress / response to light stimulus / smooth endoplasmic reticulum / anatomical structure morphogenesis / cellular response to manganese ion / heart morphogenesis / response to electrical stimulus / response to salt stress / response to amphetamine / visual perception / response to nutrient levels / ferric iron binding / fatty acid metabolic process / learning / response to activity / locomotory behavior / cellular response to glucose stimulus / animal organ morphogenesis / ferrous iron binding / terminal bouton / cytoplasmic side of plasma membrane / memory / cellular response to growth factor stimulus / cerebral cortex development / response to peptide hormone / oxygen binding / cellular response to nicotine / cellular response to xenobiotic stimulus / synaptic vesicle / response to estradiol / heart development / cytoplasmic vesicle / perikaryon / response to ethanol / response to lipopolysaccharide / response to hypoxia / neuron projection / protein domain specific binding / axon / dendrite / perinuclear region of cytoplasm / enzyme binding / mitochondrion / identical protein binding / nucleus / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.6 Å | |||||||||
![]() | Bueno-Carrasco, M.T. / Cuellar, J. / Santiago, C. / Valpuesta, J.M. / Martinez, A. / Flydal, M.I. | |||||||||
資金援助 | ![]() ![]()
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![]() | ![]() タイトル: Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation. 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 / ...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 / ![]() ![]() ![]() 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. | |||||||||
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構造の表示
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 271.1 KB | 表示 | ![]() |
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PDB形式 | ![]() | 215.4 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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非結晶学的対称性 (NCS) | NCSドメイン:
NCSドメイン領域:
NCSアンサンブル:
NCS oper:
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要素
#1: タンパク質 | 分子量: 38087.766 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #2: タンパク質・ペプチド | 分子量: 1874.081 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #3: 化合物 | ChemComp-LDP / #4: 化合物 | ChemComp-FE / 研究の焦点であるリガンドがあるか | N | |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: Tyrosine hydroxylase lacking the first 35 residues in complex with its inhibitor dopamine タイプ: COMPLEX / Entity ID: #1-#2 / 由来: RECOMBINANT | |||||||||||||||
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由来(天然) | 生物種: ![]() | |||||||||||||||
由来(組換発現) | 生物種: ![]() ![]() | |||||||||||||||
緩衝液 | pH: 7 | |||||||||||||||
緩衝液成分 |
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試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | |||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: UltrAuFoil R1.2/1.3 | |||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 95 % / 凍結前の試料温度: 277 K |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 倍率(公称値): 81000 X / 最大 デフォーカス(公称値): 3000 nm / 最小 デフォーカス(公称値): 1200 nm / Cs: 2.7 mm / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 30 e/Å2 / 検出モード: COUNTING / フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 撮影したグリッド数: 1 / 実像数: 13213 |
電子光学装置 | エネルギーフィルター名称: GIF Quantum LS |
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解析
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EMソフトウェア |
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 1626575 | ||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 4.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 152128 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||||||||
精密化 | 交差検証法: NONE 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 274.56 Å2 | ||||||||||||||||||||||||||||||||||||||||||
拘束条件 |
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Refine LS restraints NCS |
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