Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Substrate recognition and cleavage mechanism of the monkeypox virus core protease.
Journal, issue, pages	Nature, Vol. 643, Issue 8070, Page 271-279, Year 2025
Publish date	Apr 22, 2025
Authors	Yan Gao / Xiong Xie / Xiaoyu Zhang / Junyuan Cao / Weiqi Lan / Tian You / Dongxu Li / Xuxue Dong / Wenhao Dai / Yingchun Xiang / Shulei Hu / Weijuan Shang / Botao Wu / Yumin Zhang / Jin Xu / Xiaoce Liu / Haofeng Wang / Wanlong Hu / Mingjing Zhang / Yinkai Duan / Wen Cui / Hao Zhou / Shengjiang Mao / Handi Jia / Zhanqi Sun / Menghan Jia / Yue Yin / Henry C Nguyen / Kailin Yang / Bei Yang / Xiuna Yang / Xiaoyun Ji / Gengfu Xiao / Wei Wang / Leike Zhang / Zihe Rao / Hong Liu / Haitao Yang /
PubMed Abstract	Poxviruses cause severe diseases, including smallpox and mpox, that pose major threats to human health. The poxvirus core protease (Core) is essential for viral maturation and is highly conserved in ...Poxviruses cause severe diseases, including smallpox and mpox, that pose major threats to human health. The poxvirus core protease (Core) is essential for viral maturation and is highly conserved in poxviruses, making it an attractive antiviral target. However, the structure of Core remains unknown, hampering antiviral development. Here we determined the apo structure of monkeypox virus (MPXV) Core and the structure of Core in a complex with the inhibitor aloxistatin, a drug candidate for muscular dystrophy. These structures show that Core forms a homodimer that features a unique 'dancing couple' fold. The catalytic intermediate state of Core was characterized by an aldehyde derivative from a natural substrate (I-G18). This derivative binds covalently to the catalytic Cys328, shifting the active site of the viral protease from a closed conformation in the apo form to a favourable open conformation upon substrate binding. On the basis of the Core-I-G18 complex, we designed a series of peptidomimetic inhibitors with a nitrile warhead, which could covalently anchor with the catalytic Cys328. These compounds inhibit Core with half-maximal inhibitory concentrations of 44.9-100.3 nM, and exhibit potent and broad anti-poxvirus activity. Our studies provide a basis for designing wide-spectrum inhibitors against poxvirus infections.
External links	Nature / PubMed:40262633
Methods	EM (single particle) / X-ray diffraction
Resolution	1.895 - 3.03 Å
Structure data	61292 9jal EMDB-61292, PDB-9jal: Cryo-EM structure of MPXV core protease in complex with compound A1 Method: EM (single particle) / Resolution: 3.03 Å 61293 9jam EMDB-61293, PDB-9jam: Cryo-EM structure of MPXV core protease in complex with compound A3 Method: EM (single particle) / Resolution: 2.98 Å 61294 9jan EMDB-61294, PDB-9jan: Cryo-EM structure of MPXV protease in complex with compound A4 Method: EM (single particle) / Resolution: 2.93 Å 61300 9jaq EMDB-61300, PDB-9jaq: Cryo-EM structure of MPXV core protease in the apo-form Method: EM (single particle) / Resolution: 2.99 Å 62516 9kqv EMDB-62516, PDB-9kqv: Cryo-EM structure of MPXV core protease in complex with aloxistatin(E64d) Method: EM (single particle) / Resolution: 2.93 Å 62520 9kr6 EMDB-62520, PDB-9kr6: Cryo-EM structure of MPXV core protease in complex with the substrate derivative I-G18 Method: EM (single particle) / Resolution: 2.8 Å PDB-9ku2: Structure of taterapox core protease central domain Method: X-RAY DIFFRACTION / Resolution: 1.895 Å PDB-9ku9: Structure of mpox core protease mutant Method: X-RAY DIFFRACTION / Resolution: 2.199 Å
Chemicals	ChemComp-E6D: ethyl (3S)-3-hydroxy-4-({(2S)-4-methyl-1-[(3-methylbutyl)amino]-1-oxopentan-2-yl}amino)-4-oxobutanoate ChemComp-HOH: WATER
Source	monkeypox virus synthetic construct (others) taterapox virus
Keywords	VIRAL PROTEIN / Orthopoxviruses / mpox / Protease / Viral replication / Drug discovery / inhibitor / Monkeypox / E64D / orthopoxvirus