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7TX5

Neutron crystal structure of SARS-CoV-2 NSP3 macrodomain in complex with ADP-ribose at 293 K (C2 crystal form)

7TX5 の概要
エントリーDOI10.2210/pdb7tx5/pdb
分子名称Papain-like protease nsp3, ADENOSINE-5-DIPHOSPHORIBOSE (3 entities in total)
機能のキーワードsars-cov-2, room temperature diffraction, protein dynamics, water networks, viral protein
由来する生物種Severe acute respiratory syndrome coronavirus 2
タンパク質・核酸の鎖数1
化学式量合計18778.04
構造登録者
Correy, G.J.,Fraser, J.S.,Kovalevsky, A. (登録日: 2022-02-07, 公開日: 2022-02-23, 最終更新日: 2023-10-25)
主引用文献Correy, G.J.,Kneller, D.W.,Phillips, G.,Pant, S.,Russi, S.,Cohen, A.E.,Meigs, G.,Holton, J.M.,Gahbauer, S.,Thompson, M.C.,Ashworth, A.,Coates, L.,Kovalevsky, A.,Meilleur, F.,Fraser, J.S.
The mechanisms of catalysis and ligand binding for the SARS-CoV-2 NSP3 macrodomain from neutron and x-ray diffraction at room temperature.
Sci Adv, 8:eabo5083-eabo5083, 2022
Cited by
PubMed Abstract: The nonstructural protein 3 (NSP3) macrodomain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Mac1) removes adenosine diphosphate (ADP) ribosylation posttranslational modifications, playing a key role in the immune evasion capabilities of the virus responsible for the coronavirus disease 2019 pandemic. Here, we determined neutron and x-ray crystal structures of the SARS-CoV-2 NSP3 macrodomain using multiple crystal forms, temperatures, and pHs, across the apo and ADP-ribose-bound states. We characterize extensive solvation in the Mac1 active site and visualize how water networks reorganize upon binding of ADP-ribose and non-native ligands, inspiring strategies for displacing waters to increase the potency of Mac1 inhibitors. Determining the precise orientations of active site water molecules and the protonation states of key catalytic site residues by neutron crystallography suggests a catalytic mechanism for coronavirus macrodomains distinct from the substrate-assisted mechanism proposed for human MacroD2. These data provoke a reevaluation of macrodomain catalytic mechanisms and will guide the optimization of Mac1 inhibitors.
PubMed: 35622909
DOI: 10.1126/sciadv.abo5083
主引用文献が同じPDBエントリー
実験手法
NEUTRON DIFFRACTION (2.3 Å)
X-RAY DIFFRACTION (1.95 Å)
構造検証レポート
Validation report summary of 7tx5
検証レポート(詳細版)ダウンロードをダウンロード

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件を2024-12-25に公開中

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