EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease.
ジャーナル・号・ページ	Nucleic Acids Res, Vol. 51, Issue 10, Page 5255-5270, Year 2023
掲載日	2023年6月9日
著者	Andre Schutzer Godoy / Aline Minalli Nakamura / Alice Douangamath / Yun Song / Gabriela Dias Noske / Victor Oliveira Gawriljuk / Rafaela Sachetto Fernandes / Humberto D Muniz Pereira / Ketllyn Irene Zagato Oliveira / Daren Fearon / Alexandre Dias / Tobias Krojer / Michael Fairhead / Alisa Powell / Louise Dunnet / Jose Brandao-Neto / Rachael Skyner / Rod Chalk / Dávid Bajusz / Miklós Bege / Anikó Borbás / György Miklós Keserű / Frank von Delft / Glaucius Oliva /
PubMed 要旨	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The NSP15 endoribonuclease enzyme, known as NendoU, is highly conserved and ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The NSP15 endoribonuclease enzyme, known as NendoU, is highly conserved and plays a critical role in the ability of the virus to evade the immune system. NendoU is a promising target for the development of new antiviral drugs. However, the complexity of the enzyme's structure and kinetics, along with the broad range of recognition sequences and lack of structural complexes, hampers the development of inhibitors. Here, we performed enzymatic characterization of NendoU in its monomeric and hexameric form, showing that hexamers are allosteric enzymes with a positive cooperative index, and with no influence of manganese on enzymatic activity. Through combining cryo-electron microscopy at different pHs, X-ray crystallography and biochemical and structural analysis, we showed that NendoU can shift between open and closed forms, which probably correspond to active and inactive states, respectively. We also explored the possibility of NendoU assembling into larger supramolecular structures and proposed a mechanism for allosteric regulation. In addition, we conducted a large fragment screening campaign against NendoU and identified several new allosteric sites that could be targeted for the development of new inhibitors. Overall, our findings provide insights into the complex structure and function of NendoU and offer new opportunities for the development of inhibitors.
リンク	Nucleic Acids Res / PubMed:37115000 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	1.64 - 3.27 Å
構造データ	23786 7me0 EMDB-23786, PDB-7me0: Cryo-EM structure of SARS-CoV-2 NSP15 NendoU at pH 6.0 手法: EM (単粒子) / 解像度: 2.48 Å 24391 7rb0 EMDB-24391, PDB-7rb0: Cryo-EM structure of SARS-CoV-2 NSP15 NendoU at pH 7.5 手法: EM (単粒子) / 解像度: 2.98 Å 24392 7rb2 EMDB-24392, PDB-7rb2: Cryo-EM structure of SARS-CoV-2 NSP15 NendoU in BIS-Tris pH 6.0 手法: EM (単粒子) / 解像度: 3.27 Å PDB-5s6x: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z2889976755 手法: X-RAY DIFFRACTION / 解像度: 2.32 Å PDB-5s6y: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z56900771 手法: X-RAY DIFFRACTION / 解像度: 2.32 Å PDB-5s6z: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with PB2255187532 手法: X-RAY DIFFRACTION / 解像度: 2.28 Å PDB-5s70: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with EN300-181428 手法: X-RAY DIFFRACTION / 解像度: 2.327 Å PDB-5s71: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with FUZS-5 手法: X-RAY DIFFRACTION / 解像度: 1.941 Å PDB-5s72: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with BBL029427 手法: X-RAY DIFFRACTION / 解像度: 2.512 Å PDB-5sa4: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z239136710 手法: X-RAY DIFFRACTION / 解像度: 2.046 Å PDB-5sa5: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z1530301542 手法: X-RAY DIFFRACTION / 解像度: 2.09 Å PDB-5sa6: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z2856434783 手法: X-RAY DIFFRACTION / 解像度: 2.517 Å PDB-5sa7: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z1673618163 手法: X-RAY DIFFRACTION / 解像度: 2.222 Å PDB-5sa8: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z68299550 手法: X-RAY DIFFRACTION / 解像度: 2.298 Å PDB-5sa9: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z2697514548 手法: X-RAY DIFFRACTION / 解像度: 1.92 Å PDB-5saa: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z319891284 手法: X-RAY DIFFRACTION / 解像度: 2.239 Å PDB-5sab: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z31504642 手法: X-RAY DIFFRACTION / 解像度: 2.486 Å PDB-5sac: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z59181945 手法: X-RAY DIFFRACTION / 解像度: 2.029 Å PDB-5sad: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z425449682 手法: X-RAY DIFFRACTION / 解像度: 1.961 Å PDB-5sae: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z3219959731 手法: X-RAY DIFFRACTION / 解像度: 2.12 Å PDB-5saf: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with EN300-321461 手法: X-RAY DIFFRACTION / 解像度: 2.11 Å PDB-5sag: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with EN300-1605072 手法: X-RAY DIFFRACTION / 解像度: 1.881 Å PDB-5sah: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with EN300-100112 手法: X-RAY DIFFRACTION / 解像度: 2.16 Å PDB-5sai: PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 NendoU in complex with Z1424343998 手法: X-RAY DIFFRACTION / 解像度: 2.022 Å PDB-5sbf: PanDDA analysis group deposition of ground-state model of SARS-CoV-2 NendoU 手法: X-RAY DIFFRACTION / 解像度: 1.64 Å PDB-7keg: Crystal structure from SARS-COV2 NendoU NSP15 手法: X-RAY DIFFRACTION / 解像度: 2.9 Å PDB-7keh: Crystal structure from SARS-CoV-2 NendoU NSP15 手法: X-RAY DIFFRACTION / 解像度: 2.59 Å PDB-7kf4: Crystal structure from SARS-CoV-2 NendoU NSP15 手法: X-RAY DIFFRACTION / 解像度: 2.61 Å PDB-7n7r: Crystal Structure of SARS-CoV-2 NendoU in complex with Z2472938267 手法: X-RAY DIFFRACTION / 解像度: 2.01 Å PDB-7n7u: Crystal Structure of SARS-CoV-2 NendoU in complex with LIZA-7 手法: X-RAY DIFFRACTION / 解像度: 2.06 Å PDB-7n7w: Crystal Structure of SARS-CoV-2 NendoU in complex with CSC000178569 手法: X-RAY DIFFRACTION / 解像度: 2.42 Å PDB-7n7y: Crystal Structure of SARS-CoV-2 NendoU in complex with Z18197050 手法: X-RAY DIFFRACTION / 解像度: 2.09 Å PDB-7n83: Crystal Structure of SARS-CoV-2 NendoU in complex with Z2443429438 手法: X-RAY DIFFRACTION / 解像度: 1.91 Å
化合物	ChemComp-CIT: CITRIC ACID / クエン酸 / クエン酸 ChemComp-WUG: 1-(2,4-dimethyl-1H-imidazol-5-yl)methanamine ChemComp-HOH: WATER / 水 ChemComp-WUJ: N-[(furan-2-yl)methyl]urea / N-フルフリル尿素 ChemComp-WUM: 4-[(dimethylamino)methyl]-1,3-thiazol-2-amine ChemComp-WUS: (5R)-2-methyl-4,5,6,7-tetrahydro-1H-benzimidazol-5-amine ChemComp-WUV: 5'-thiothymidine / 5′-メルカプト-5′-デオキシチミジン ChemComp-WUY: N-(2-aminoethyl)-N'-phenylurea / 1-(2-アミノエチル)-3-フェニル尿素 ChemComp-K3A: N-(5-methyl-1H-pyrazol-3-yl)acetamide / 3-(アセチルアミノ)-5-メチル-1H-ピラゾ-ル ChemComp-ZQA: 4-ethyl-2-(1H-imidazol-5-yl)-1,3-thiazole ChemComp-O3G: N-benzyl-1-(4-fluorophenyl)methanamine / ベンジル(4-フルオロベンジル)アミン ChemComp-WL7: 4-amino-N-(2-hydroxyethyl)-N-methylbenzene-1-sulfonamide ChemComp-JOV: 3-chloro-N-(1-hydroxy-2-methylpropan-2-yl)benzamide ChemComp-GWG: 1-methylindazole-3-carboxamide ChemComp-ZQD: 3-[(2S)-1-(methanesulfonyl)pyrrolidin-2-yl]-5-methyl-1,2-oxazole ChemComp-WJD: 2-methoxy-N-phenylacetamide ChemComp-VWG: N-hydroxyquinoline-2-carboxamide / 2-キノリンカルボヒドロキシム酸 ChemComp-EJW: (3-phenyl-1,2-oxazol-5-yl)methylazanium ChemComp-W3G: pyridazin-3(2H)-one / ピリダジン-3(2H)-オン ChemComp-WOY: 6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine ChemComp-ZQG: 3-(1H-imidazol-2-yl)propan-1-amine ChemComp-ZQJ: 2-methyl-5,6,7,8-tetrahydropyrido[4,3-c]pyridazin-3(2H)-one ChemComp-ZQM: N-{2-[(propan-2-yl)sulfanyl]phenyl}urea ChemComp-PO4: PHOSPHATE ION / ホスファ-ト / リン酸塩 ChemComp-B3P: 2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL / 2,2′-(トリメチレンビスイミノ)ビス[2-(ヒドロキシメチル)プロパン-1,3-ジオ-ル] / pH緩衝剤YM / Bis-tris propane ChemComp-SO4: SULFATE ION / 硫酸ジアニオン / 硫酸塩 ChemComp-S6V: 1-[2-(2-oxidanylidenepyrrolidin-1-yl)ethyl]-3-phenyl-urea ChemComp-0MI: 1-[(2~{R},4~{S},5~{R})-5-[[(azanylidene-$l^{4}-azanylidene)amino]methyl]-4-oxidanyl-oxolan-2-yl]-5-methyl-pyrimidine-2,4-dione ChemComp-0OI: N-(2-fluorophenyl)-N'-methylurea / 1-メチル-3-(2-フルオロフェニル)尿素 ChemComp-RZG: methyl 4-sulfamoylbenzoate / 4-スルファモイル安息香酸メチル ChemComp-WNM*: (3S)-1-(phenylsulfonyl)pyrrolidin-3-amine
由来	severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2)
キーワード	HYDROLASE (加水分解酵素) / SGC - Diamond I04-1 fragment screening / PanDDA / XChemExplorer / nsp15 / nendoU / sars-cov-2 (SARSコロナウイルス2) / sars (重症急性呼吸器症候群) / covid (新型コロナウイルス感染症 (2019年)) / covid19 (新型コロナウイルス感染症 (2019年)) / HYDROLASE/HYDROLASE inhibitor / HYDROLASE-HYDROLASE inhibitor complex / VIRAL PROTEIN (ウイルスタンパク質) / covid-19 (新型コロナウイルス感染症 (2019年)) / endoribonuclease / coronavirus (オルトコロナウイルス亜科)