[日本語] English
万見
- PDB-9gl9: Wild-type EGFR bound with STX-721 -

+
データを開く


IDまたはキーワード:

読み込み中...

-
基本情報

登録情報
データベース: PDB / ID: 9gl9
タイトルWild-type EGFR bound with STX-721
要素Epidermal growth factor receptor
キーワードTRANSFERASE / Kinase / Inhibitor
機能・相同性
機能・相同性情報


positive regulation of protein kinase C activity / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / response to hydroxyisoflavone / diterpenoid metabolic process / Shc-EGFR complex / Inhibition of Signaling by Overexpressed EGFR / ovulation cycle / EGFR interacts with phospholipase C-gamma ...positive regulation of protein kinase C activity / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / response to hydroxyisoflavone / diterpenoid metabolic process / Shc-EGFR complex / Inhibition of Signaling by Overexpressed EGFR / ovulation cycle / EGFR interacts with phospholipase C-gamma / positive regulation of mucus secretion / epidermal growth factor binding / regulation of peptidyl-tyrosine phosphorylation / response to UV-A / tongue development / PLCG1 events in ERBB2 signaling / midgut development / ERBB2-EGFR signaling pathway / digestive tract morphogenesis / hydrogen peroxide metabolic process / morphogenesis of an epithelial fold / PTK6 promotes HIF1A stabilization / ERBB2 Activates PTK6 Signaling / Signaling by EGFR / intracellular vesicle / response to cobalamin / negative regulation of epidermal growth factor receptor signaling pathway / eyelid development in camera-type eye / cerebral cortex cell migration / protein insertion into membrane / ERBB2 Regulates Cell Motility / protein tyrosine kinase activator activity / Signaling by ERBB4 / Respiratory syncytial virus (RSV) attachment and entry / PI3K events in ERBB2 signaling / negative regulation of mitotic cell cycle / MAP kinase kinase kinase activity / hair follicle development / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / positive regulation of G1/S transition of mitotic cell cycle / GAB1 signalosome / positive regulation of bone resorption / embryonic placenta development / positive regulation of phosphorylation / salivary gland morphogenesis / peptidyl-tyrosine autophosphorylation / positive regulation of peptidyl-serine phosphorylation / positive regulation of glial cell proliferation / positive regulation of vasoconstriction / Signaling by ERBB2 / transmembrane receptor protein tyrosine kinase activity / GRB2 events in EGFR signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / GRB2 events in ERBB2 signaling / cellular response to epidermal growth factor stimulus / SHC1 events in ERBB2 signaling / cellular response to dexamethasone stimulus / positive regulation of synaptic transmission, glutamatergic / ossification / positive regulation of DNA repair / neuron projection morphogenesis / positive regulation of superoxide anion generation / positive regulation of epithelial cell proliferation / epithelial cell proliferation / liver regeneration / basal plasma membrane / Signal transduction by L1 / positive regulation of DNA replication / positive regulation of protein localization to plasma membrane / astrocyte activation / phosphatidylinositol 3-kinase/protein kinase B signal transduction / NOTCH3 Activation and Transmission of Signal to the Nucleus / cellular response to amino acid stimulus / positive regulation of smooth muscle cell proliferation / cellular response to estradiol stimulus / lung development / EGFR downregulation / synaptic membrane / clathrin-coated endocytic vesicle membrane / Signaling by ERBB2 TMD/JMD mutants / placental growth factor receptor activity / insulin receptor activity / vascular endothelial growth factor receptor activity / Constitutive Signaling by EGFRvIII / hepatocyte growth factor receptor activity / macrophage colony-stimulating factor receptor activity / platelet-derived growth factor alpha-receptor activity / platelet-derived growth factor beta-receptor activity / stem cell factor receptor activity / boss receptor activity / protein tyrosine kinase collagen receptor activity / brain-derived neurotrophic factor receptor activity / transmembrane-ephrin receptor activity / GPI-linked ephrin receptor activity / epidermal growth factor receptor activity / fibroblast growth factor receptor activity / insulin-like growth factor receptor activity / Signaling by ERBB2 ECD mutants
類似検索 - 分子機能
: / Epidermal growth factor receptor transmembrane-juxtamembrane segment / Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain ...: / Epidermal growth factor receptor transmembrane-juxtamembrane segment / Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / Furin-like repeat / Furin-like repeats / Growth factor receptor cysteine-rich domain superfamily / : / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
類似検索 - ドメイン・相同性
: / Epidermal growth factor receptor
類似検索 - 構成要素
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: 2.147 Å
データ登録者Hilbert, B.J. / Brooijmans, N. / Milgram, B.C. / Pagliarini, R.A.
資金援助1件
組織認可番号国
Not funded
引用ジャーナル: Clin.Cancer Res. / 年: 2025
タイトル: STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20-Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models.
著者: Pagliarini, R.A. / Henderson, J.A. / Milgram, B.C. / Borrelli, D.R. / Brooijmans, N. / Hilbert, B.J. / Huff, M.R. / Ito, T. / Kryukov, G.V. / Ladd, B. / Martin, B.R. / Motiwala, H. / O'Hearn, ...著者: Pagliarini, R.A. / Henderson, J.A. / Milgram, B.C. / Borrelli, D.R. / Brooijmans, N. / Hilbert, B.J. / Huff, M.R. / Ito, T. / Kryukov, G.V. / Ladd, B. / Martin, B.R. / Motiwala, H. / O'Hearn, E. / Tsai, C.F. / Wang, W. / Bellier, J. / Boland, L. / Clark, S. / Hensley, E. / Hata, A.N. / Kuzmic, P. / Guzman-Perez, A. / Jackson, E.L. / Stuart, D.D.
履歴
登録2024年8月27日登録サイト: PDBE / 処理サイト: PDBE
改定 1.02025年5月14日Provider: repository / タイプ: Initial release
改定 1.12025年6月11日Group: Database references / カテゴリ: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

-
構造の表示

構造ビューア分子:
MolmilJmol/JSmol

ダウンロードとリンク

-
集合体

登録構造単位
A: Epidermal growth factor receptor
ヘテロ分子


分子量 (理論値)分子数
合計 (水以外)38,2234
ポリマ－37,5631
非ポリマー6603
水3,819212
1


  • 登録構造と同一
  • 登録者・ソフトウェアが定義した集合体
タイプ名称対称操作数
identity operation1_555x,y,z1
Buried area220 Å2
ΔGint-14 kcal/mol
Surface area15650 Å2
手法PISA
単位格子
Length a, b, c (Å)145.765, 145.765, 145.765
Angle α, β, γ (deg.)90, 90, 90
Int Tables number197
Space group name H-MI23

-
要素

#1: タンパク質 Epidermal growth factor receptor / Proto-oncogene c-ErbB-1 / Receptor tyrosine-protein kinase erbB-1


分子量: 37563.457 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: EGFR, ERBB, ERBB1, HER1
発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ)
参照: UniProt: P00533, receptor protein-tyrosine kinase
#2: 化合物 ChemComp-CL / CHLORIDE ION / クロリド


分子量: 35.453 Da / 分子数: 2 / 由来タイプ: 合成 / 式: Cl
#3: 化合物 ChemComp-A1IMT / (2R,3S)-3-[(3-chloranyl-2-methoxy-phenyl)amino]-2-[3-[2-[(2R)-1-[(E)-4-(dimethylamino)but-2-enoyl]-2-methyl-pyrrolidin-2-yl]ethynyl]pyridin-4-yl]-1,2,3,5,6,7-hexahydropyrrolo[3,2-c]pyridin-4-one


分子量: 589.128 Da / 分子数: 1 / 由来タイプ: 合成 / 式: C32H37ClN6O3 / タイプ: SUBJECT OF INVESTIGATION
#4: 水 ChemComp-HOH / water


分子量: 18.015 Da / 分子数: 212 / 由来タイプ: 天然 / 式: H2O
研究の焦点であるリガンドがあるかY
Has protein modificationY

-
実験情報

-
実験

実験手法: X線回折 / 使用した結晶の数: 1

-
試料調製

結晶マシュー密度: 3.44 Å3/Da / 溶媒含有率: 64.2 %
結晶化温度: 285 K / 手法: 蒸気拡散法, ハンギングドロップ法
詳細: 0.1 M HEPES-NaOH pH 6.9, 0.98 M Sodium Succinate pH 7.0, 5 mM TCEP

-
データ収集

回折平均測定温度: 100 K / Serial crystal experiment: N
放射光源由来: シンクロトロン / サイト: SLS / ビームライン: X06SA / 波長: 1.000011 Å
検出器タイプ: DECTRIS EIGER X 16M / 検出器: PIXEL / 日付: 2023年4月21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: 1.000011 Å / 相対比: 1
反射解像度: 2.147→34.357 Å / Num. obs: 27574 / % possible obs: 97.8 % / 冗長度: 10.45 %
詳細: Some remarks regarding the mmCIF items written, the PDB Exchange Dictionary (PDBx/mmCIF) Version 5.0 supporting the data files in the current PDB archive (dictionary version 5.325, last ...詳細: Some remarks regarding the mmCIF items written, the PDB Exchange Dictionary (PDBx/mmCIF) Version 5.0 supporting the data files in the current PDB archive (dictionary version 5.325, last updated 2020-04-13: http://mmcif.wwpdb.org/dictionaries/mmcif_pdbx_v50.dic/Index/) and the actual quantities provided by MRFANA (https://github.com/githubgphl/MRFANA) from the autoPROC package (https://www.globalphasing.com/autoproc/). In general, the mmCIF categories here should provide items that are currently used in the PDB archive. If there are alternatives, the one recommended by the PDB developers has been selected. The distinction between *_all and *_obs quantities is not always clear: often only one version is actively used within the PDB archive (or is the one recommended by PDB developers). The intention of distinguishing between classes of reflections before and after some kind of observation criterion was applied, can in principle be useful - but such criteria change in various ways throughout the data processing steps (rejection of overloaded or too partial reflections, outlier/misfit rejections during scaling etc) and there is no retrospect computation of data scaling/merging statistics for the reflections used in the final refinement (where another observation criterion might have been applied). Typical data processing will usually only provide one version of statistics at various stages and these are given in the recommended item here, irrespective of the "_all" and "_obs" connotation, see e.g. the use of _reflns.pdbx_Rmerge_I_obs, _reflns.pdbx_Rrim_I_all and _reflns.pdbx_Rpim_I_all. Please note that all statistics related to "merged intensities" (or "merging") are based on inverse-variance weighting of the individual measurements making up a symmetry-unique reflection. This is standard for several decades now, even if some of the dictionary definitions seem to suggest that a simple "mean" or "average" intensity is being used instead. R-values are always given for all symmetry-equivalent reflections following Friedel's law, i.e. Bijvoet pairs are not treated separately (since we want to describe the overall mean intensity and not the mean I(+) and I(-) here). The Rrim metric is identical to the Rmeas R-value and only differs in name. _reflns.pdbx_number_measured_all is the number of measured intensities just before the final merging step (at which point no additional rejection takes place). _reflns.number_obs is the number of symmetry-unique observations, i.e. the result of merging those measurements via inverse-variance weighting. _reflns.pdbx_netI_over_sigmaI is based on the merged intensities (_reflns.number_obs) as expected. _reflns.pdbx_redundancy is synonymous with "multiplicity". The per-shell item _reflns_shell.number_measured_all corresponds to the overall value _reflns.pdbx_number_measured_all. The per-shell item _reflns_shell.number_unique_all corresponds to the overall value _reflns.number_obs. The per-shell item _reflns_shell.percent_possible_all corresponds to the overall value _reflns.percent_possible_obs. The per-shell item _reflns_shell.meanI_over_sigI_obs corresponds to the overall value given as _reflns.pdbx_netI_over_sigmaI. But be aware of the incorrect definition of the former in the current dictionary!
CC1/2: 0.999 / CC1/2 anomalous: 0.006 / Rmerge(I) obs: 0.0721 / Rpim(I) all: 0.0234 / Rrim(I) all: 0.0759 / AbsDiff over sigma anomalous: 0.751 / Net I/σ(I): 18.25 / Num. measured all: 288086 / % possible anomalous: 97.6 / Redundancy anomalous: 5.4
反射 シェル
解像度 (Å)冗長度 (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. measured obsNum. unique allNum. unique obsCC1/2CC1/2 anomalousRpim(I) allRrim(I) allAbsDiff over sigma anomalous% possible anomalousRedundancy anomalous% possible all
4.622-34.35710.050.034549.232952629526293829380.999-0.0050.01140.03630.7831005.31100
3.67-4.62210.470.041443.762820828208269426940.9990.0420.01340.04360.76194.15.4594.7
3.206-3.6710.670.063131.352486124861232923290.998-0.1050.02030.06630.77581.65.5582.1
2.913-3.20610.930.101720.953057130571279827980.9970.0330.03210.10670.7841005.63100
2.705-2.9139.930.165512.952803428034282328230.993-0.0230.05510.17460.7691005.11100
2.545-2.7059.950.24489.212780027800279427940.984-0.0370.08130.25820.76399.95.12100
2.418-2.54510.440.38556.252932329323281028100.963-0.0440.12470.40550.7111005.37100
2.313-2.41810.620.53634.572954029540278227820.941-0.0080.17190.56350.7241005.45100
2.224-2.31310.690.78083.353008730087281528150.8830.020.24970.82020.7471005.48100
2.147-2.22410.81.03682.493013630136279127910.818-0.0140.32961.08840.6971005.52100

-
解析

ソフトウェア
名称バージョン分類
autoPROC1.1.7 20230222data processing
XDSJan 10, 2022データ削減
Aimless0.7.9データスケーリング
TRUNCATE8.0.011data processing
PHASER位相決定
BUSTER2.11.8精密化
精密化構造決定の手法: 分子置換 / 解像度: 2.147→34.36 Å / Cor.coef. Fo:Fc: 0.952 / Cor.coef. Fo:Fc free: 0.948 / SU R Cruickshank DPI: 0.289 / 交差検証法: THROUGHOUT / SU R Blow DPI: 0.182 / SU Rfree Blow DPI: 0.148 / SU Rfree Cruickshank DPI: 0.146
Rfactor反射数%反射Selection details
Rfree0.2128 1152 -RANDOM
Rwork0.1968 ---
obs0.1975 27574 97.7 %-
原子変位パラメータBiso mean: 56.71 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å20 Å2
3---0 Å2
Refine analyzeLuzzati coordinate error obs: 0.25 Å
精密化ステップサイクル: LAST / 解像度: 2.147→34.36 Å
タンパク質核酸リガンド溶媒全体
原子数2520 0 44 212 2776
拘束条件
Refine-IDタイプDev ideal数Restraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.015234HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.049505HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1563SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes792HARMONIC5
X-RAY DIFFRACTIONt_it2648HARMONIC10
X-RAY DIFFRACTIONt_nbd0SEMIHARMONIC5
X-RAY DIFFRACTIONt_chiral_improper_torsion339SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact4717SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion3.56
X-RAY DIFFRACTIONt_other_torsion15.58
LS精密化 シェル解像度: 2.15→2.16 Å
Rfactor反射数%反射
Rfree0.2403 23 -
Rwork0.2402 --
obs0.2402 552 100 %
精密化 TLSOrigin x: 24.5719 Å / Origin y: 8.0303 Å / Origin z: 58.9529 Å
111213212223313233
T-0.0579 Å20.0294 Å20.0312 Å2-0.0074 Å2-0.0569 Å2---0.0014 Å2
L0.4744 °2-0.4221 °2-0.2809 °2-1.7518 °20.402 °2--0.6599 °2
S0.1344 Å °-0.1284 Å °-0.007 Å °-0.1284 Å °-0.0754 Å °-0.0685 Å °-0.007 Å °-0.0685 Å °-0.059 Å °
精密化 TLSグループ
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|* }A694 - 1019
2X-RAY DIFFRACTION1{ A|* }A1031 - 2001

+
万見について

-
お知らせ

-
2022年2月9日: EMDBエントリの付随情報ファイルのフォーマットが新しくなりました

EMDBエントリの付随情報ファイルのフォーマットが新しくなりました

  • EMDBのヘッダファイルのバージョン3が、公式のフォーマットとなりました。
  • これまでは公式だったバージョン1.9は、アーカイブから削除されます。

関連情報:EMDBヘッダ

外部リンク:wwPDBはEMDBデータモデルのバージョン3へ移行します

-
2020年8月12日: 新型コロナ情報

新型コロナ情報

URL: https://pdbj.org/emnavi/covid19.php

新ページ: EM Navigatorに新型コロナウイルスの特設ページを開設しました。

関連情報:Covid-19情報 / 2020年3月5日: 新型コロナウイルスの構造データ

+
2020年3月5日: 新型コロナウイルスの構造データ

新型コロナウイルスの構造データ

関連情報:万見生物種 / 2020年8月12日: 新型コロナ情報

外部リンク:COVID-19特集ページ - PDBj / 今月の分子2020年2月：コロナウイルスプロテーアーゼ

+
2019年1月31日: EMDBのIDの桁数の変更

EMDBのIDの桁数の変更

  • EMDBエントリに付与されているアクセスコード(EMDB-ID)は4桁の数字(例、EMD-1234)でしたが、間もなく枯渇します。これまでの4桁のID番号は4桁のまま変更されませんが、4桁の数字を使い切った後に発行されるIDは5桁以上の数字(例、EMD-12345)になります。5桁のIDは2019年の春頃から発行される見通しです。
  • EM Navigator/万見では、接頭語「EMD-」は省略されています。

関連情報:Q: 「EMD」とは何ですか？ / 万見/EM NavigatorにおけるID/アクセスコードの表記

外部リンク:EMDB Accession Codes are Changing Soon! / PDBjへお問い合わせ

+
2017年7月12日: PDB大規模アップデート

PDB大規模アップデート

  • 新バージョンのPDBx/mmCIF辞書形式に基づくデータがリリースされました。
  • 今回の更新はバージョン番号が4から5になる大規模なもので、全エントリデータの書き換えが行われる「Remediation」というアップデートに該当します。
  • このバージョンアップで、電子顕微鏡の実験手法に関する多くの項目の書式が改定されました(例：em_softwareなど)。
  • EM NavigatorとYorodumiでも、この改定に基づいた表示内容になります。

外部リンク:wwPDB Remediation / OneDepデータ基準に準拠した、より強化された内容のモデル構造ファイルが、PDBアーカイブで公開されました。

-
万見 (Yorodumi)

幾万の構造データを、幾万の視点から

  • 万見(Yorodumi)は、EMDB/PDB/SASBDBなどの構造データを閲覧するためのページです。
  • EM Navigatorの詳細ページの後継、Omokage検索のフロントエンドも兼ねています。

関連情報:EMDB / PDB / SASBDB / 3つのデータバンクの比較 / 万見検索 / 2016年8月31日: 新しいEM Navigatorと万見 / 万見文献 / Jmol/JSmol / 機能・相同性情報 / 新しいEM Navigatorと万見の変更点

他の情報も見る