7MHL

Ensemble refinement structure of SARS-CoV-2 main protease (Mpro) at 100 K

7MHL の概要

• エントリーDOI: 10.2210/pdb7mhl/pdb
• 関連するPDBエントリー: 7MHF 7MHG 7MHH 7MHI 7MHJ 7MHK 7MHM 7MHN 7MHO 7MHP 7MHQ
• 分子名称: 3C-like proteinase, DIMETHYL SULFOXIDE, ZINC ION, ... (4 entities in total)
• 機能のキーワード: sars-cov-2, coronavirus, main protease, 3clpro, mpro, hydrolase, ensemble refinement, temperature series, temperature, multitemperature
• 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: 34281.62

構造登録者

Ebrahim, A.,Riley, B.T.,Kumaran, D.,Andi, B.,Fuchs, M.R.,McSweeney, S.,Keedy, D.A. (登録日: 2021-04-15, 公開日: 2021-05-12, 最終更新日: 2023-10-25)

主引用文献

Ebrahim, A.,Riley, B.T.,Kumaran, D.,Andi, B.,Fuchs, M.R.,McSweeney, S.,Keedy, D.A.
The tem-per-ature-dependent conformational ensemble of SARS-CoV-2 main protease (M pro ).
Iucrj, 9:682-694, 2022

PubMed Abstract: The COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or M, is a promising target for the development of novel antiviral therapeutics. Previous X-ray crystal structures of M were obtained at cryogenic tem-per-ature or room tem-per-ature only. Here we report a series of high-resolution crystal structures of unliganded M across multiple tem-per-atures from cryogenic to physiological, and another at high humidity. We inter-rogate these data sets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a perturbation-dependent conformational landscape for M, including a mobile zinc ion inter-leaved between the catalytic dyad, mercurial conformational heterogeneity at various sites including a key substrate-binding loop, and a far-reaching intra-molecular network bridging the active site and dimer inter-face. Our results may inspire new strategies for antiviral drug development to aid preparation for future coronavirus pandemics.

PubMed: 36071812
DOI: 10.1107/S2052252522007497

実験手法

X-RAY DIFFRACTION (1.55 Å)