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基本情報
登録情報 | データベース: PDB / ID: 7d4f | |||||||||||||||||||||||||||||||||||||||
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タイトル | Structure of COVID-19 RNA-dependent RNA polymerase bound to suramin | |||||||||||||||||||||||||||||||||||||||
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![]() | VIRAL PROTEIN / COVID-19 / RNA polymerase / suramin binding | |||||||||||||||||||||||||||||||||||||||
機能・相同性 | ![]() protein guanylyltransferase activity / RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / 付加脱離酵素(リアーゼ); P-Oリアーゼ類; - / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Maturation of replicase proteins / ISG15-specific peptidase activity / TRAF3-dependent IRF activation pathway ...protein guanylyltransferase activity / RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / 付加脱離酵素(リアーゼ); P-Oリアーゼ類; - / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Maturation of replicase proteins / ISG15-specific peptidase activity / TRAF3-dependent IRF activation pathway / Transcription of SARS-CoV-2 sgRNAs / snRNP Assembly / Translation of Replicase and Assembly of the Replication Transcription Complex / Replication of the SARS-CoV-2 genome / 加水分解酵素; エステル加水分解酵素; 5'-リン酸モノエステル産生エキソリボヌクレアーゼ / host cell endoplasmic reticulum-Golgi intermediate compartment / double membrane vesicle viral factory outer membrane / SARS coronavirus main proteinase / 5'-3' DNA helicase activity / 3'-5'-RNA exonuclease activity / host cell endosome / symbiont-mediated degradation of host mRNA / mRNA guanylyltransferase / symbiont-mediated suppression of host ISG15-protein conjugation / symbiont-mediated suppression of host toll-like receptor signaling pathway / G-quadruplex RNA binding / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity / omega peptidase activity / mRNA (guanine-N7)-methyltransferase / SARS-CoV-2 modulates host translation machinery / methyltransferase cap1 / host cell Golgi apparatus / symbiont-mediated suppression of host NF-kappaB cascade / symbiont-mediated perturbation of host ubiquitin-like protein modification / DNA helicase / methyltransferase cap1 activity / ubiquitinyl hydrolase 1 / cysteine-type deubiquitinase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; システインプロテアーゼ / single-stranded RNA binding / host cell perinuclear region of cytoplasm / regulation of autophagy / viral protein processing / lyase activity / host cell endoplasmic reticulum membrane / RNA helicase / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / symbiont-mediated suppression of host gene expression / copper ion binding / viral translational frameshifting / symbiont-mediated activation of host autophagy / RNA-directed RNA polymerase / cysteine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / DNA-templated transcription / lipid binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell nucleus / ATP hydrolysis activity / proteolysis / RNA binding / zinc ion binding / ATP binding / membrane 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: 2.57 Å | |||||||||||||||||||||||||||||||||||||||
![]() | Li, Z. / Yin, W. / Zhou, Z. / Yu, X. / Xu, H. | |||||||||||||||||||||||||||||||||||||||
![]() | ![]() タイトル: Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin. 著者: Wanchao Yin / Xiaodong Luan / Zhihai Li / Ziwei Zhou / Qingxing Wang / Minqi Gao / Xiaoxi Wang / Fulai Zhou / Jingjing Shi / Erli You / Mingliang Liu / Qingxia Wang / Yi Jiang / Hualiang ...著者: Wanchao Yin / Xiaodong Luan / Zhihai Li / Ziwei Zhou / Qingxing Wang / Minqi Gao / Xiaoxi Wang / Fulai Zhou / Jingjing Shi / Erli You / Mingliang Liu / Qingxia Wang / Yi Jiang / Hualiang Jiang / Gengfu Xiao / Leike Zhang / Xuekui Yu / Shuyang Zhang / H Eric Xu / ![]() 要旨: The COVID-19 pandemic caused by nonstop infections of SARS-CoV-2 has continued to ravage many countries worldwide. Here we report that suramin, a 100-year-old drug, is a potent inhibitor of the SARS- ...The COVID-19 pandemic caused by nonstop infections of SARS-CoV-2 has continued to ravage many countries worldwide. Here we report that suramin, a 100-year-old drug, is a potent inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and acts by blocking the binding of RNA to the enzyme. In biochemical assays, suramin and its derivatives are at least 20-fold more potent than remdesivir, the currently approved nucleotide drug for treatment of COVID-19. The 2.6 Å cryo-electron microscopy structure of the viral RdRp bound to suramin reveals two binding sites. One site directly blocks the binding of the RNA template strand and the other site clashes with the RNA primer strand near the RdRp catalytic site, thus inhibiting RdRp activity. Suramin blocks viral replication in Vero E6 cells, although the reasons underlying this effect are likely various. Our results provide a structural mechanism for a nonnucleotide inhibitor of the SARS-CoV-2 RdRp. | |||||||||||||||||||||||||||||||||||||||
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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 | ![]() | 224.7 KB | 表示 | ![]() |
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PDB形式 | ![]() | 175.3 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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-検証レポート
文書・要旨 | ![]() | 1.1 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.1 MB | 表示 | |
XML形式データ | ![]() | 35.8 KB | 表示 | |
CIF形式データ | ![]() | 57 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-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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要素
#1: タンパク質 | 分子量: 22034.242 Da / 分子数: 2 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() 遺伝子: rep, 1a-1b 発現宿主: ![]() ![]() 参照: UniProt: P0DTD1 #2: タンパク質 | | 分子量: 9380.000 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() 遺伝子: rep, 1a-1b 発現宿主: ![]() ![]() 参照: UniProt: P0DTD1 #3: タンパク質 | | 分子量: 107965.250 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() 遺伝子: rep, 1a-1b 発現宿主: ![]() ![]() 参照: UniProt: P0DTD1, RNA-directed RNA polymerase #4: 化合物 | #5: 化合物 | 研究の焦点であるリガンドがあるか | Y | Has protein modification | 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: COVID-19 RdRp complex bound to suramin / タイプ: COMPLEX / Entity ID: #1-#3 / 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: 7.4 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
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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 |
撮影 | 電子線照射量: 68 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.14_3260: / 分類: 精密化 |
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EMソフトウェア | 名称: PHENIX / カテゴリ: モデル精密化 |
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3次元再構成 | 解像度: 2.57 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 95845 / 対称性のタイプ: POINT |