9DU2

SARS-CoV-2 Mpro in complex with compound 7

これはPDB形式変換不可エントリーです。

9DU2 の概要

• エントリーDOI: 10.2210/pdb9du2/pdb
• 分子名称: 3C-like proteinase nsp5, N-[(2S)-3-cyclopropyl-1-{[(1Z,2S)-1-imino-4-(methanesulfonyl)butan-2-yl]amino}-1-oxopropan-2-yl]-4-methoxy-1H-indole-2-carboxamide (3 entities in total)
• 機能のキーワード: sars-cov-2 mpro hydrolase, compound 7, corona virus, aldehyde and nitrile based inhibitors, viral protein, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70952.84

構造登録者

Bigelow, L.,Tang, H.,Boguslaw, N.,Duda, D.M. (登録日: 2024-10-02, 公開日: 2025-04-30, 最終更新日: 2025-08-06)

主引用文献

Padmanabha Das, K.M.,Chen, J.,Charifson, P.S.,Green, J.,Tang, H.,Panchal, S.,Pu, F.,Korepanova, A.,Dubey, A.,Afanador, G.,Stojkovic, V.,Nocek, B.,Bigelow, L.,Stubbs, S.H.,Davey, R.A.,DeGoey, D.A.,Arthanari, H.,Namchuk, M.N.
Inhibition of dimeric SARS-CoV-2 Mpro displays positive cooperativity and a mixture of covalent and non-covalent binding.
Iscience, 28:112773-112773, 2025

PubMed Abstract: SARS-CoV-2 Mpro is a cysteine protease that acts as a symmetrical dimer and displays positive cooperativity for substrate turnover. A series of potent reversible covalent peptidomimetic aldehydes and nitriles was designed as Mpro inhibitors. To better understand the observed structure activity relationships (SAR), binding potency and mechanism was examined by enzyme activity assay, surface plasmon resonance, X-ray crystallography, matrix-assisted laser desorption electrospray ionization, and nuclear magnetic resonance (NMR). Potent aldehydes bind Mpro cooperativity but bind covalently to only one subunit of the dimer. The analogous nitriles do not bind cooperatively, and the degree of covalent binding observed varied depending on the assay method employed. The NMR studies support that potent inhibition of Mpro by the nitriles does not require covalent binding. The data highlight the caveats in using orthogonal assays to confirm compound mechanism, particularly in cooperative systems.

PubMed: 40655098
DOI: 10.1016/j.isci.2025.112773

実験手法

X-RAY DIFFRACTION (1.86 Å)