6XBG

Crystal structure of the SARS-CoV-2 (COVID-19) main protease in complex with inhibitor UAW246

6XBG の概要

• エントリーDOI: 10.2210/pdb6xbg/pdb
• 関連するBIRD辞書のPRD_ID: PRD_002392
• 分子名称: 3C-like proteinase, inhibitor UAW246, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: covid, covid19, covid-19, sars, sars cov2, cov, ncov 19, coronavirus, main protease, 3cl, mpro, pro, viral protein, gc376, calpain inhibitor ii, leupeptin, calpain, aldehyde, gc-376, 3cl-like, a-ketoamide, uaw41, uaw246, uaw247, uaw248, 246, 247, 248, alpheketoamide, alpha, ketoamide, peptidomimetic, protease, cysteine, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 69466.20

構造登録者

Sacco, M.,Ma, C.,Wang, J.,Chen, Y. (登録日: 2020-06-05, 公開日: 2020-06-17, 最終更新日: 2024-11-13)

主引用文献

Sacco, M.D.,Ma, C.,Lagarias, P.,Gao, A.,Townsend, J.A.,Meng, X.,Dube, P.,Zhang, X.,Hu, Y.,Kitamura, N.,Hurst, B.,Tarbet, B.,Marty, M.T.,Kolocouris, A.,Xiang, Y.,Chen, Y.,Wang, J.
Structure and inhibition of the SARS-CoV-2 main protease reveal strategy for developing dual inhibitors against M pro and cathepsin L.
Sci Adv, 6:-, 2020

PubMed Abstract: The main protease (M) of SARS-CoV-2 is a key antiviral drug target. While most M inhibitors have a γ-lactam glutamine surrogate at the P1 position, we recently found that several M inhibitors have hydrophobic moieties at the P1 site, including calpain inhibitors II and XII, which are also active against human cathepsin L, a host protease that is important for viral entry. In this study, we solved x-ray crystal structures of M in complex with calpain inhibitors II and XII and three analogs of The structure of M with calpain inhibitor II confirmed that the S1 pocket can accommodate a hydrophobic methionine side chain, challenging the idea that a hydrophilic residue is necessary at this position. The structure of calpain inhibitor XII revealed an unexpected, inverted binding pose. Together, the biochemical, computational, structural, and cellular data presented herein provide new directions for the development of dual inhibitors as SARS-CoV-2 antivirals.

PubMed: 33158912
DOI: 10.1126/sciadv.abe0751

実験手法

X-RAY DIFFRACTION (1.45 Å)