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- PDB-8sc8: Structure of PI3KG in complex with MTX-531 -

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基本情報

登録情報
データベース: PDB / ID: 8sc8
タイトルStructure of PI3KG in complex with MTX-531
要素Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
キーワードTRANSFERASE/INHIBITOR / PI3KG / dual EGFR/PI3K inhibitor / TRANSFERASE / TRANSFERASE-INHIBITOR complex
機能・相同性
機能・相同性情報


negative regulation of triglyceride catabolic process / secretory granule localization / natural killer cell chemotaxis / neutrophil extravasation / phosphatidylinositol-4-phosphate 3-kinase / positive regulation of acute inflammatory response / respiratory burst involved in defense response / negative regulation of cardiac muscle contraction / regulation of calcium ion transmembrane transport / T cell chemotaxis ...negative regulation of triglyceride catabolic process / secretory granule localization / natural killer cell chemotaxis / neutrophil extravasation / phosphatidylinositol-4-phosphate 3-kinase / positive regulation of acute inflammatory response / respiratory burst involved in defense response / negative regulation of cardiac muscle contraction / regulation of calcium ion transmembrane transport / T cell chemotaxis / negative regulation of fibroblast apoptotic process / phosphatidylinositol 3-kinase complex, class IB / sphingosine-1-phosphate receptor signaling pathway / phosphatidylinositol 3-kinase complex, class IA / dendritic cell chemotaxis / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / phosphatidylinositol-4,5-bisphosphate 3-kinase / phosphatidylinositol 3-kinase / phosphatidylinositol-3-phosphate biosynthetic process / 1-phosphatidylinositol-3-kinase activity / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / mast cell degranulation / hepatocyte apoptotic process / positive regulation of Rac protein signal transduction / regulation of cell adhesion mediated by integrin / Synthesis of PIPs at the plasma membrane / phosphatidylinositol-mediated signaling / phosphatidylinositol phosphate biosynthetic process / regulation of angiogenesis / phosphorylation / T cell proliferation / cellular response to cAMP / GPVI-mediated activation cascade / ephrin receptor binding / neutrophil chemotaxis / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of endothelial cell migration / T cell activation / positive regulation of cytokine production / positive regulation of MAP kinase activity / platelet aggregation / endocytosis / G beta:gamma signalling through PI3Kgamma / kinase activity / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / angiogenesis / adaptive immune response / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / non-specific serine/threonine protein kinase / protein kinase activity / inflammatory response / immune response / G protein-coupled receptor signaling pathway / innate immune response / protein serine kinase activity / protein serine/threonine kinase activity / ATP binding / identical protein binding / membrane / plasma membrane / cytosol / cytoplasm
類似検索 - 分子機能
PIK3 catalytic subunit gamma, adaptor-binding domain / PIK3 catalytic subunit gamma adaptor-binding domain / Phosphatidylinositol 3-kinase, adaptor-binding domain / Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain profile. / PI3-kinase family, Ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain / PI3-kinase family, ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain profile. / C2 phosphatidylinositol 3-kinase-type domain / Phosphoinositide 3-kinase C2 ...PIK3 catalytic subunit gamma, adaptor-binding domain / PIK3 catalytic subunit gamma adaptor-binding domain / Phosphatidylinositol 3-kinase, adaptor-binding domain / Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain profile. / PI3-kinase family, Ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain / PI3-kinase family, ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain profile. / C2 phosphatidylinositol 3-kinase-type domain / Phosphoinositide 3-kinase C2 / C2 phosphatidylinositol 3-kinase (PI3K)-type domain profile. / Phosphoinositide 3-kinase, region postulated to contain C2 domain / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Phosphoinositide 3-kinase, accessory (PIK) domain superfamily / Phosphoinositide 3-kinase, accessory (PIK) domain / Phosphatidylinositol kinase / PIK helical domain profile. / Phosphatidylinositol 3- and 4-kinases signature 1. / Phosphatidylinositol 3- and 4-kinases signature 2. / Phosphatidylinositol 3/4-kinase, conserved site / Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / C2 domain superfamily / Armadillo-type fold / Ubiquitin-like domain superfamily / Protein kinase-like domain superfamily
類似検索 - ドメイン・相同性
: / Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
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 / フーリエ合成 / 解像度: 2.687 Å
データ登録者Whitehead, C.E. / Leopold, J.
資金援助1件
組織認可番号
Not funded
引用ジャーナル: To Be Published
タイトル: Structure of PI3KG in complex with MTX-531
著者: Whitehead, C.E. / Leopold, J.
履歴
登録2023年4月5日登録サイト: RCSB / 処理サイト: RCSB
改定 1.02024年6月12日Provider: repository / タイプ: Initial release

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構造の表示

構造ビューア分子:
MolmilJmol/JSmol

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集合体

登録構造単位
A: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
ヘテロ分子


分子量 (理論値)分子数
合計 (水以外)111,6617
ポリマ-110,7271
非ポリマー9346
1,60389
1


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  • 登録者が定義した集合体
タイプ名称対称操作
identity operation1_555x,y,z1
単位格子
Length a, b, c (Å)143.934, 67.452, 106.983
Angle α, β, γ (deg.)90.000, 95.274, 90.000
Int Tables number5
Space group name H-MC121

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要素

#1: タンパク質 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform / PtdIns-3-kinase subunit gamma / Phosphatidylinositol 4 / 5-bisphosphate 3-kinase 110 kDa catalytic ...PtdIns-3-kinase subunit gamma / Phosphatidylinositol 4 / 5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma / p110gamma / Phosphoinositide-3-kinase catalytic gamma polypeptide / Serine/threonine protein kinase PIK3CG / p120-PI3K


分子量: 110727.102 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: PIK3CG
発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ)
参照: UniProt: P48736, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
#2: 化合物
ChemComp-SO4 / SULFATE ION / 硫酸ジアニオン


分子量: 96.063 Da / 分子数: 5 / 由来タイプ: 合成 / : SO4
#3: 化合物 ChemComp-D0D / N-[(5P)-2-chloro-5-(4-{[(1R)-1-phenylethyl]amino}quinazolin-6-yl)pyridin-3-yl]methanesulfonamide


分子量: 453.945 Da / 分子数: 1 / 由来タイプ: 合成 / : C22H20ClN5O2S / タイプ: SUBJECT OF INVESTIGATION
#4: 水 ChemComp-HOH / water


分子量: 18.015 Da / 分子数: 89 / 由来タイプ: 天然 / : H2O
研究の焦点であるリガンドがあるかY

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実験情報

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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: 2.34 Å3/Da / 溶媒含有率: 47.33 %
結晶化温度: 293 K / 手法: 蒸気拡散法, ハンギングドロップ法 / pH: 8.2
詳細: 0.2 M Lithium Sulfate, 0.1 M TRIS-HCl pH 8.2, 15% w/v PEG 4000

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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: ESRF / ビームライン: MASSIF-1 / 波長: 0.965459 Å
検出器タイプ: DECTRIS PILATUS3 2M / 検出器: PIXEL / 日付: 2022年11月11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: 0.965459 Å / 相対比: 1
反射解像度: 2.687→33.726 Å / Num. obs: 23452 / % possible obs: 91.6 % / 冗長度: 6.1 %
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: 0.998 / CC1/2 anomalous: -0.362 / Rmerge(I) obs: 0.0717 / Rpim(I) all: 0.0316 / Rrim(I) all: 0.0785 / AbsDiff over sigma anomalous: 0.692 / Baniso tensor eigenvalue 1: 23.0769 Å2 / Baniso tensor eigenvalue 2: 18.3309 Å2 / Baniso tensor eigenvalue 3: 0 Å2 / Baniso tensor eigenvector 1 ortho1: 0.8302 / Baniso tensor eigenvector 1 ortho2: 0 / Baniso tensor eigenvector 1 ortho3: 0.5575 / Baniso tensor eigenvector 2 ortho1: 0 / Baniso tensor eigenvector 2 ortho2: 1 / Baniso tensor eigenvector 2 ortho3: 0 / Baniso tensor eigenvector 3 ortho1: -0.5575 / Baniso tensor eigenvector 3 ortho2: 0 / Baniso tensor eigenvector 3 ortho3: 0.8302 / Aniso diffraction limit 1: 2.977 Å / Aniso diffraction limit 2: 2.734 Å / Aniso diffraction limit 3: 2.68 Å / Aniso diffraction limit axis 1 ortho1: 0.90037 / Aniso diffraction limit axis 1 ortho2: 0 / Aniso diffraction limit axis 1 ortho3: 0.43509 / Aniso diffraction limit axis 2 ortho1: 0 / Aniso diffraction limit axis 2 ortho2: 1 / Aniso diffraction limit axis 2 ortho3: 0 / Aniso diffraction limit axis 3 ortho1: -0.43509 / Aniso diffraction limit axis 3 ortho2: 0 / Aniso diffraction limit axis 3 ortho3: 0.90037 / Net I/σ(I): 13.96 / Num. measured all: 143017 / Observed signal threshold: 1.2 / Orthogonalization convention: pdb / % possible anomalous: 91 / % possible ellipsoidal: 91.6 / % possible ellipsoidal anomalous: 91 / % possible spherical: 81.6 / % possible spherical anomalous: 81 / Redundancy anomalous: 3.15 / Signal type: local
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 anomalous% possible ellipsoidal% possible ellipsoidal anomalous% possible spherical% possible spherical anomalousRedundancy anomalous% possible all
6.248-33.7265.480.032534.851284712847234423440.998-0.4770.01460.03570.60799.299.299.299.299.22.9399.2
4.94-6.2486.110.04929.151432914329234623460.996-0.4160.02150.05370.66599.710099.710099.73.18100
4.315-4.945.680.053625.721331213312234523450.996-0.2240.02470.05920.71599.499.799.499.799.42.9599.7
3.915-4.3155.990.079719.151404814048234523450.995-0.2330.03550.08750.7159910099100993.12100
3.631-3.9156.390.13512.721499414994234623460.99-0.1070.0580.14710.71799.699.999.699.999.63.2899.9
3.416-3.6316.520.23287.841528715287234423440.975-0.0050.09880.25330.71699.799.999.799.999.73.3599.9
3.242-3.4166.660.40444.631560615606234523450.9350.0260.16930.43890.70599.810099.810099.83.41100
3.101-3.2426.290.68142.61476714767234723470.820.0030.29510.74380.68799.810099.810099.83.23100
2.975-3.1015.811.04831.571362313623234423440.6440.0210.47591.15390.70295.595.795.595.795.52.9895.7
2.687-2.9756.051.22061.341420414204234623460.5470.0040.54141.33770.68853.153.753.131.331.13.153.7

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解析

ソフトウェア
名称バージョン分類
autoPROC1.1.7 20220608data processing
XDSJan 10, 2022データ削減
Aimless0.7.9データスケーリング
STARANISO2.3.87データスケーリング
REFMAC5.8.0352精密化
REFMAC5.8.0352位相決定
精密化構造決定の手法: フーリエ合成 / 解像度: 2.687→33.726 Å / Cor.coef. Fo:Fc: 0.957 / Cor.coef. Fo:Fc free: 0.917 / SU B: 37.351 / SU ML: 0.351 / 交差検証法: FREE R-VALUE / ESU R Free: 0.412 / 詳細: Hydrogens have been added in their riding positions
Rfactor反射数%反射
Rfree0.2533 1194 5.091 %
Rwork0.1951 22258 -
all0.198 --
obs-23452 81.564 %
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 BULK SOLVENT
原子変位パラメータBiso mean: 98.219 Å2
Baniso -1Baniso -2Baniso -3
1--2.476 Å2-0 Å2-1.306 Å2
2--0.87 Å2-0 Å2
3---1.816 Å2
精密化ステップサイクル: LAST / 解像度: 2.687→33.726 Å
タンパク質核酸リガンド溶媒全体
原子数6708 0 56 89 6853
拘束条件
Refine-IDタイプDev idealDev ideal target
X-RAY DIFFRACTIONr_bond_refined_d0.0030.0126914
X-RAY DIFFRACTIONr_bond_other_d0.0010.0166432
X-RAY DIFFRACTIONr_angle_refined_deg0.8121.6539361
X-RAY DIFFRACTIONr_angle_other_deg0.2831.57114984
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.2255818
X-RAY DIFFRACTIONr_dihedral_angle_2_deg3.283540
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.885101248
X-RAY DIFFRACTIONr_dihedral_angle_6_deg13.01310320
X-RAY DIFFRACTIONr_chiral_restr0.0370.21055
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.027650
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021357
X-RAY DIFFRACTIONr_nbd_refined0.1870.21428
X-RAY DIFFRACTIONr_symmetry_nbd_other0.1750.26370
X-RAY DIFFRACTIONr_nbtor_refined0.1740.23345
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0740.23681
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1370.2165
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_other0.0070.21
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1060.29
X-RAY DIFFRACTIONr_nbd_other0.1160.246
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.0380.22
X-RAY DIFFRACTIONr_mcbond_it2.5387.013302
X-RAY DIFFRACTIONr_mcbond_other2.5367.0113302
X-RAY DIFFRACTIONr_mcangle_it4.36710.4984110
X-RAY DIFFRACTIONr_mcangle_other4.36710.4984111
X-RAY DIFFRACTIONr_scbond_it2.1517.23612
X-RAY DIFFRACTIONr_scbond_other2.1517.2013613
X-RAY DIFFRACTIONr_scangle_it3.7210.7095251
X-RAY DIFFRACTIONr_scangle_other3.7210.715252
X-RAY DIFFRACTIONr_lrange_it6.76781.7497704
X-RAY DIFFRACTIONr_lrange_other6.76681.747703
LS精密化 シェル
解像度 (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.687-2.7560.50250.26875X-RAY DIFFRACTION3.8204
2.756-2.8310.264240.371318X-RAY DIFFRACTION16.6019
2.831-2.9130.417550.336847X-RAY DIFFRACTION45.88
2.913-3.0020.34720.3071437X-RAY DIFFRACTION78.5528
3.002-3.0990.335920.2861734X-RAY DIFFRACTION97.5949
3.099-3.2070.252880.2641761X-RAY DIFFRACTION100
3.207-3.3270.333990.2461634X-RAY DIFFRACTION100
3.327-3.4610.294900.2311617X-RAY DIFFRACTION99.9415
3.461-3.6140.287750.2171531X-RAY DIFFRACTION99.9378
3.614-3.7880.235800.1941483X-RAY DIFFRACTION99.9361
3.788-3.990.272680.1881434X-RAY DIFFRACTION99.9335
3.99-4.2280.216750.1631292X-RAY DIFFRACTION99.9269
4.228-4.5150.227660.1661255X-RAY DIFFRACTION99.6229
4.515-4.870.218620.1651172X-RAY DIFFRACTION99.8382
4.87-5.3230.236530.1821094X-RAY DIFFRACTION100
5.323-5.9330.223660.189961X-RAY DIFFRACTION100
5.933-6.8160.241470.204885X-RAY DIFFRACTION99.8928
6.816-8.2640.225340.179748X-RAY DIFFRACTION98.8622
8.264-11.3520.197240.144606X-RAY DIFFRACTION98.9011
11.352-33.7260.399190.214374X-RAY DIFFRACTION99.7462
精密化 TLS手法: refined / Origin x: 32.5494 Å / Origin y: -1.1008 Å / Origin z: 25.9238 Å
111213212223313233
T0.2863 Å2-0.0196 Å20.0763 Å2-0.0091 Å2-0.0094 Å2--0.0507 Å2
L3.7308 °20.6721 °20.6408 °2-0.5783 °20.1366 °2--1.3675 °2
S-0.0485 Å °-0.0078 Å °-0.2724 Å °0.0036 Å °0.058 Å °-0.0859 Å °-0.2369 Å °0.021 Å °-0.0095 Å °
精密化 TLSグループSelection: ALL

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  • 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

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