+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7mx7 | ||||||
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タイトル | PRMT5:MEP50 complexed with inhibitor PF-06939999 | ||||||
要素 |
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キーワード | TRANSFERASE/Transcription / arginine (アルギニン) / methyl (メチル基) / transferase (転移酵素) / TRANSFERASE-Transcription complex | ||||||
機能・相同性 | 機能・相同性情報 positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway / peptidyl-arginine N-methylation / oocyte axis specification / type II protein arginine methyltransferase / protein-arginine omega-N symmetric methyltransferase activity / peptidyl-arginine methylation / Golgi ribbon formation / negative regulation of epithelial cell proliferation involved in prostate gland development / histone H4R3 methyltransferase activity / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development ...positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway / peptidyl-arginine N-methylation / oocyte axis specification / type II protein arginine methyltransferase / protein-arginine omega-N symmetric methyltransferase activity / peptidyl-arginine methylation / Golgi ribbon formation / negative regulation of epithelial cell proliferation involved in prostate gland development / histone H4R3 methyltransferase activity / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development / histone arginine N-methyltransferase activity / epithelial cell proliferation involved in prostate gland development / : / methylosome / protein-arginine N-methyltransferase activity / methyl-CpG binding / endothelial cell activation / histone H3 methyltransferase activity / positive regulation of mRNA splicing, via spliceosome / Cul4B-RING E3 ubiquitin ligase complex / histone methyltransferase complex / regulation of mitotic nuclear division / positive regulation of oligodendrocyte differentiation / histone methyltransferase activity / E-box binding / negative regulation of cell differentiation / ubiquitin-like ligase-substrate adaptor activity / spliceosomal snRNP assembly / ribonucleoprotein complex binding / regulation of ERK1 and ERK2 cascade / nuclear receptor coactivator activity / regulation of signal transduction by p53 class mediator / methyltransferase activity / liver regeneration / DNA-templated transcription termination / circadian regulation of gene expression / Regulation of TP53 Activity through Methylation / RMTs methylate histone arginines / protein polyubiquitination / transcription corepressor activity / p53 binding / snRNP Assembly / ubiquitin-dependent protein catabolic process / クロマチンリモデリング / protein heterodimerization activity / クロマチン / positive regulation of cell population proliferation / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / ゴルジ体 / 核質 / identical protein binding / 細胞核 / 細胞質基質 / 細胞質 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | X線回折 / シンクロトロン / 分子置換 / 解像度: 2.49 Å | ||||||
データ登録者 | McTigue, M. / Deng, Y.L. / Liu, W. / Brooun, A. | ||||||
引用 | ジャーナル: Mol.Cancer Ther. / 年: 2022 タイトル: SAM-Competitive PRMT5 Inhibitor PF-06939999 Demonstrates Antitumor Activity in Splicing Dysregulated NSCLC with Decreased Liability of Drug Resistance. 著者: Jensen-Pergakes, K. / Tatlock, J. / Maegley, K.A. / McAlpine, I.J. / McTigue, M. / Xie, T. / Dillon, C.P. / Wang, Y. / Yamazaki, S. / Spiegel, N. / Shi, M. / Nemeth, A. / Miller, N. / ...著者: Jensen-Pergakes, K. / Tatlock, J. / Maegley, K.A. / McAlpine, I.J. / McTigue, M. / Xie, T. / Dillon, C.P. / Wang, Y. / Yamazaki, S. / Spiegel, N. / Shi, M. / Nemeth, A. / Miller, N. / Hendrickson, E. / Lam, H. / Sherrill, J. / Chung, C.Y. / McMillan, E.A. / Bryant, S.K. / Palde, P. / Braganza, J. / Brooun, A. / Deng, Y.L. / Goshtasbi, V. / Kephart, S.E. / Kumpf, R.A. / Liu, W. / Patman, R.L. / Rui, E. / Scales, S. / Tran-Dube, M. / Wang, F. / Wythes, M. / Paul, T.A. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7mx7.cif.gz | 204.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7mx7.ent.gz | 158.5 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7mx7.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/mx/7mx7 ftp://data.pdbj.org/pub/pdb/validation_reports/mx/7mx7 | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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単位格子 |
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-要素
#1: タンパク質 | 分子量: 72766.664 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PRMT5, HRMT1L5, IBP72, JBP1, SKB1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: O14744, type II protein arginine methyltransferase |
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#2: タンパク質 | 分子量: 39520.082 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: WDR77, MEP50, WD45, HKMT1069, Nbla10071 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q9BQA1 |
#3: 化合物 | ChemComp-ZR1 / ( |
#4: 水 | ChemComp-HOH / |
研究の焦点であるリガンドがあるか | Y |
-実験情報
-実験
実験 | 手法: X線回折 / 使用した結晶の数: 1 |
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-試料調製
結晶 | マシュー密度: 2.77 Å3/Da / 溶媒含有率: 55.62 % |
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結晶化 | 温度: 286.15 K / 手法: 蒸気拡散法 詳細: Crystallization of full-length human PRMT5/MEP50 complexed with cofactor site inhibitors was performed at 13 degrees Celsius by hanging-drop vapor-diffusion methods. 2.5 ul of a solution of 5: ...詳細: Crystallization of full-length human PRMT5/MEP50 complexed with cofactor site inhibitors was performed at 13 degrees Celsius by hanging-drop vapor-diffusion methods. 2.5 ul of a solution of 5:1 molar ratio of inhibitor compound to PRMT5/MEP50 complex (13 mg/mL) was mixed with 2.5 ul of reservoir solution containing 13-15% (w/v) PEG3350, 0.1M MES, pH 6.5-7.5, 0.25M NaCl, and 20% (v/v) ethylene glycol. Microseeding from initial crystals produced crystals suitable for data collection. Crystals for data collection were flash-frozen in liquid N2 using 25% (v/v) ethylene glycol in the mother liquor as a cryoprotectant |
-データ収集
回折 | 平均測定温度: 95 K / Serial crystal experiment: N |
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放射光源 | 由来: シンクロトロン / サイト: APS / ビームライン: 17-ID / 波長: 1 Å |
検出器 | タイプ: DECTRIS PILATUS 6M / 検出器: PIXEL / 日付: 2016年12月14日 |
放射 | プロトコル: SINGLE WAVELENGTH / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray |
放射波長 | 波長: 1 Å / 相対比: 1 |
反射 | 解像度: 2.49→89.13 Å / Num. obs: 44025 / % possible obs: 99.9 % / 冗長度: 6.7 % / Rmerge(I) obs: 0.064 / Rpim(I) all: 0.027 / Rrim(I) all: 0.069 / Net I/σ(I): 19.3 |
反射 シェル | 解像度: 2.49→2.62 Å / 冗長度: 6.9 % / Rmerge(I) obs: 0.682 / Mean I/σ(I) obs: 2.2 / Num. unique obs: 6374 / Rpim(I) all: 0.278 / Rrim(I) all: 0.737 |
-解析
ソフトウェア |
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精密化 | 構造決定の手法: 分子置換 開始モデル: 4GQB 解像度: 2.49→89.13 Å / Cor.coef. Fo:Fc: 0.845 / Cor.coef. Fo:Fc free: 0.794 / SU R Cruickshank DPI: 0.414 / 交差検証法: THROUGHOUT / SU R Blow DPI: 0.416 / SU Rfree Blow DPI: 0.286 / SU Rfree Cruickshank DPI: 0.289
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原子変位パラメータ | Biso mean: 70.8 Å2
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Refine analyze | Luzzati coordinate error obs: 0.45 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: LAST / 解像度: 2.49→89.13 Å
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拘束条件 |
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LS精密化 シェル | 解像度: 2.49→2.51 Å
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