9PAA

Crystal structure of HCoV-229E 3CLpro with ALG-0987608 (inhibitor 1)

これはPDB形式変換不可エントリーです。

9PAA の概要

• エントリーDOI: 10.2210/pdb9paa/pdb
• 分子名称: 3C-like proteinase, (1R,2R,3S,6S,7S)-4-[(2S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl]-10,10-difluoro-N-{(1E,2R)-1-imino-3-[(3R)-2-oxo-3,4-dihydro-2H-pyrrol-3-yl]propan-2-yl}-4-azatricyclo[5.2.1.0~2,6~]decane-3-carboxamide (non-preferred name), DODECAETHYLENE GLYCOL, ... (4 entities in total)
• 機能のキーワード: hydrolase/inhibitor, hcov 229e, 3clprotease, mpro, nsp5, alg-097608, pan coronovirus durg, viral protein
• 由来する生物種: Human coronavirus 229E
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67580.63

構造登録者

Reddem, E.R.,Forouhad, F.,Shapiro, L.,Stoycheva, A. (登録日: 2025-06-25, 公開日: 2026-02-11, 最終更新日: 2026-04-15)

主引用文献

Reddem, E.R.,Forouhar, F.,Liu, C.,Stevens, S.K.,Jekle, A.,Chang, C.W.,Oswal, N.,McGowan, D.C.,Vandyck, K.,Smith, D.B.,Raboisson, P.,Beigelman, L.N.,Katsamba, P.S.,Bahna, F.,Mannepalli, S.,Blatt, L.,Perlin, D.,Symons, J.A.,Shapiro, L.,Stoycheva, A.D.
Structural basis for pan-coronavirus inhibition of 3CL protease.
Structure, 34:562-571.e8, 2026

PubMed Abstract: Epidemic and pandemic outbreaks of respiratory illness caused by three different coronaviruses over the past two decades have underscored the importance of pharmaceutical agents that could offer broad-spectrum activity across this family of pathogens. Two coronavirus inhibitors characterized by broad in vitro potency were synthesized and studied with X-ray crystallography. Their high-resolution structures in complex with six α-, β-, and γ-coronaviruses delineate the requirements for pan-coronavirus inhibition by drug-like molecules targeting the S1-S4 subsites of the viral 3CL-protease, which performs a critical function during coronavirus polyprotein processing. Anchoring by polar contacts in S1, utilization of hydrophobic packing in S2, compact substitutions in S3, and mid-sized hydrophobic modifications in S4 are all factors contributing to inhibitor activity. Interactions in S2 are modulated by the amino acid identity of three key residues, and in S4, where sequence conservation is the lowest, pan-coronavirus coverage is facilitated by solvent exposure of the diverging side chains.

PubMed: 41650964
DOI: 10.1016/j.str.2026.01.003

実験手法

X-RAY DIFFRACTION (1.41 Å)