+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 5i4v | ||||||
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タイトル | Discovery of novel, orally efficacious Liver X Receptor (LXR) beta agonists | ||||||
要素 |
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キーワード | DNA BINDING PROTEIN (DNA結合タンパク質) / LXRbeta-LBD / RXRbeta-LBD / heterodimer / agonist (アゴニスト) | ||||||
機能・相同性 | 機能・相同性情報 positive regulation of secretion of lysosomal enzymes / positive regulation of high-density lipoprotein particle assembly / positive regulation of pancreatic juice secretion / phosphatidylcholine acyl-chain remodeling / positive regulation of cholesterol transport / negative regulation of response to endoplasmic reticulum stress / negative regulation of pinocytosis / positive regulation of lipoprotein lipase activity / apolipoprotein A-I receptor binding / positive regulation of triglyceride biosynthetic process ...positive regulation of secretion of lysosomal enzymes / positive regulation of high-density lipoprotein particle assembly / positive regulation of pancreatic juice secretion / phosphatidylcholine acyl-chain remodeling / positive regulation of cholesterol transport / negative regulation of response to endoplasmic reticulum stress / negative regulation of pinocytosis / positive regulation of lipoprotein lipase activity / apolipoprotein A-I receptor binding / positive regulation of triglyceride biosynthetic process / retinoic acid-responsive element binding / NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis / NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose / NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake / positive regulation of lipid storage / NR1H2 & NR1H3 regulate gene expression linked to lipogenesis / positive regulation of fatty acid biosynthetic process / negative regulation of lipid transport / anatomical structure development / positive regulation of vitamin D receptor signaling pathway / negative regulation of cold-induced thermogenesis / Signaling by Retinoic Acid / nuclear steroid receptor activity / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / negative regulation of type II interferon-mediated signaling pathway / negative regulation of cholesterol storage / locomotor rhythm / aryl hydrocarbon receptor binding / negative regulation of macrophage derived foam cell differentiation / regulation of lipid metabolic process / cellular response to Thyroglobulin triiodothyronine / regulation of glucose metabolic process / Synthesis of bile acids and bile salts / positive regulation of cholesterol efflux / retinoic acid receptor signaling pathway / Endogenous sterols / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / positive regulation of bone mineralization / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / nuclear retinoid X receptor binding / response to retinoic acid / regulation of cellular response to insulin stimulus / Recycling of bile acids and salts / cellular response to hormone stimulus / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / positive regulation of adipose tissue development / peroxisome proliferator activated receptor signaling pathway / RORA activates gene expression / positive regulation of protein metabolic process / VLDLR internalisation and degradation / Regulation of lipid metabolism by PPARalpha / hormone-mediated signaling pathway / BMAL1:CLOCK,NPAS2 activates circadian gene expression / Activation of gene expression by SREBF (SREBP) / SUMOylation of transcription cofactors / nuclear receptor coactivator activity / response to progesterone / cholesterol homeostasis / nuclear receptor binding / negative regulation of proteolysis / RNA polymerase II transcription regulatory region sequence-specific DNA binding / circadian regulation of gene expression / Heme signaling / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / Transcriptional activation of mitochondrial biogenesis / PPARA activates gene expression / Cytoprotection by HMOX1 / chromatin DNA binding / positive regulation of miRNA transcription / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / RNA polymerase II transcription regulator complex / nuclear receptor activity / Circadian Clock / sequence-specific double-stranded DNA binding / HATs acetylate histones / ATPase binding / DNA-binding transcription activator activity, RNA polymerase II-specific / Estrogen-dependent gene expression / transcription regulator complex / 細胞分化 / transcription coactivator activity / nuclear body / protein dimerization activity / DNA-binding transcription factor activity, RNA polymerase II-specific / RNA polymerase II cis-regulatory region sequence-specific DNA binding / protein domain specific binding / negative regulation of DNA-templated transcription / chromatin binding / クロマチン / 核小体 / regulation of DNA-templated transcription / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / protein-containing complex / DNA binding 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: 2.61 Å | ||||||
データ登録者 | Chen, G. / McKeever, B.M. | ||||||
引用 | ジャーナル: J.Med.Chem. / 年: 2016 タイトル: Discovery of a Novel, Orally Efficacious Liver X Receptor (LXR) beta Agonist. 著者: Zheng, Y. / Zhuang, L. / Fan, K.Y. / Tice, C.M. / Zhao, W. / Dong, C. / Lotesta, S.D. / Leftheris, K. / Lindblom, P.R. / Liu, Z. / Shimada, J. / Noto, P.B. / Meng, S. / Hardy, A. / Howard, L. ...著者: Zheng, Y. / Zhuang, L. / Fan, K.Y. / Tice, C.M. / Zhao, W. / Dong, C. / Lotesta, S.D. / Leftheris, K. / Lindblom, P.R. / Liu, Z. / Shimada, J. / Noto, P.B. / Meng, S. / Hardy, A. / Howard, L. / Krosky, P. / Guo, J. / Lipinski, K. / Kandpal, G. / Bukhtiyarov, Y. / Zhao, Y. / Lala, D. / Van Orden, R. / Zhou, J. / Chen, G. / Wu, Z. / McKeever, B.M. / McGeehan, G.M. / Gregg, R.E. / Claremon, D.A. / Singh, S.B. | ||||||
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 | 5i4v.cif.gz | 200.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb5i4v.ent.gz | 157.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 5i4v.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/i4/5i4v ftp://data.pdbj.org/pub/pdb/validation_reports/i4/5i4v | HTTPS FTP |
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-関連構造データ
関連構造データ | 1uhlS S: 精密化の開始モデル |
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類似構造データ |
-リンク
-集合体
登録構造単位 |
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単位格子 |
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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: Component-ID: 0 / Refine code: 0
NCSアンサンブル:
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-要素
#1: タンパク質 | 分子量: 30567.936 Da / 分子数: 2 変異: Q259A, R261G, D262S, R264S,Q259A, R261G, D262S, R264S,Q259A, R261G, D262S, R264S,Q259A, R261G, D262S, R264S 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) 遺伝子: NR1H2, LXRB, NER, UNR, NCOA2, BHLHE75, SRC2, TIF2 プラスミド: pET28a(+) / 発現宿主: Escherichia coli (大腸菌) / 株 (発現宿主): BL21(DE3) / 参照: UniProt: P55055, UniProt: Q15596 #2: タンパク質 | 分子量: 28114.312 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: RXRB, NR2B2, NCOA2, BHLHE75, SRC2, TIF2 / プラスミド: pET21a(+) / 発現宿主: Escherichia coli (大腸菌) / 株 (発現宿主): BL21(DE3) / 参照: UniProt: P28702, UniProt: Q15596 #3: 化合物 | #4: 水 | ChemComp-HOH / | |
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-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: 2.12 Å3/Da / 溶媒含有率: 41.99 % |
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結晶化 | 温度: 298 K / 手法: 蒸気拡散法, ハンギングドロップ法 / pH: 8 詳細: 1uL of scLXRbeta-LBD/scRXRbeta-LBD @ 10 mg protein/ml in 20 mM Tris-HCl pH 8.0, 150 mM NaCl, 5 mM DTT containing 1mM ligand and less than 2%(v/v) DMSO was mixed with 1uL of reservoir solution ...詳細: 1uL of scLXRbeta-LBD/scRXRbeta-LBD @ 10 mg protein/ml in 20 mM Tris-HCl pH 8.0, 150 mM NaCl, 5 mM DTT containing 1mM ligand and less than 2%(v/v) DMSO was mixed with 1uL of reservoir solution (0.2M LiCl, 16-20%(w/v) PEG3350, 7-10%(v/v) ethylene glycol, 0.01M Strontium chloride) on a circular, silanized glass cover slide and inverted and sealed with silicon grease over a well of 200uL of reservoir solution. Crystallization plates were incubated at 23 deg C for 2-5 days before rods would appear measuring 50 to 100um long. |
-データ収集
回折 | 平均測定温度: 100 K / Ambient temp details: CryoJet |
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放射光源 | 由来: シンクロトロン / サイト: NSLS / ビームライン: X29A / 波長: 1.075 Å |
検出器 | タイプ: ADSC QUANTUM 315r / 検出器: CCD / 日付: 2011年4月8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: 1.075 Å / 相対比: 1 |
反射 | 解像度: 2.609→82.67 Å / Num. obs: 29640 / % possible obs: 95.25 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / 冗長度: 12.2 % / Biso Wilson estimate: 59.14 Å2 / Net I/σ(I): 13.3 |
反射 シェル | 解像度: 2.609→2.68 Å / 冗長度: 5.5 % / Mean I/σ(I) obs: 1.24 / % possible all: 71.3 |
-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: 1UHL 解像度: 2.61→47.72 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.924 / SU B: 33.343 / SU ML: 0.315 / 交差検証法: THROUGHOUT / ESU R Free: 0.349 / 立体化学のターゲット値: MAXIMUM LIKELIHOOD / 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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溶媒の処理 | イオンプローブ半径: 0.8 Å / 減衰半径: 0.8 Å / VDWプローブ半径: 1.2 Å / 溶媒モデル: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 47.114 Å2
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精密化ステップ | サイクル: LAST / 解像度: 2.61→47.72 Å
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拘束条件 |
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