Deciphering Allosteric Modulation of Cancer-Associated Histone Missense Mutations DOI Creative Commons
Shuxiang Li, Jie Shu,

James C. Rober

и другие.

Journal of Molecular Biology, Год журнала: 2025, Номер unknown, С. 169180 - 169180

Опубликована: Апрель 1, 2025

Язык: Английский

Structural and Mechanistic Insights into the Main Protease (Mpro) Dimer Interface Destabilization Inhibitor: Unveiling New Therapeutic Avenues against SARS-CoV-2 DOI
Ankur Singh,

Kuldeep Jangid,

Sanketkumar Nehul

и другие.

Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

SARS-CoV-2 variant recurrence has emphasized the imperative prerequisite for effective antivirals. The main protease (Mpro) of is crucial viral replication, making it one prime and promising antiviral targets. Mpro features several druggable sites, including active sites allosteric near dimerization interface, that regulate its catalytic activity. This study identified six highly efficacious compounds (WIN-62577, KT185, bexarotene, ledipasvir, diacerein, simepervir) using structure-based virtual screening compound libraries against Mpro. Using SPR ITC, binding selected inhibitory to target was validated. FRET-based assay demonstrated molecules effectively inhibit with IC50 values in range from 0.64 11.98 μM. Additionally, vitro cell-based assays showed high efficacy EC50 1.51 18.92 crystal structure Mpro-minocycline complex detailed possible inhibition mechanism minocycline, an FDA-approved antibiotic. Minocycline binds site, revealing residues critical loss activity due destabilization molecular interactions at dimeric which are proteolytic suggests minocycline site may play a role dimer direct rational design derivatives as drugs.

Язык: Английский

Процитировано

1
Allostery in Disease: Anticancer Drugs, Pockets, and the Tumor Heterogeneity Challenge DOI Creative Commons
Ruth Nussinov, Bengi Ruken Yavuz, Hyunbum Jang

и другие.

Journal of Molecular Biology, Год журнала: 2025, Номер unknown, С. 169050 - 169050

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
The Evolving Landscape of Protein Allostery: From Computational and Experimental Perspectives DOI

E. Srinivasan,

Grigor Arakelov, Nikolay V. Dokholyan

и другие.

Journal of Molecular Biology, Год журнала: 2025, Номер unknown, С. 169060 - 169060

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Dynamic Coupling and Entropy Changes in KRAS G12D Mutation: Insights into Molecular Flexibility, Allostery and Function DOI
Aysima Hacisuleyman, Deniz Yüret, Burak Erman

и другие.

Journal of Molecular Biology, Год журнала: 2025, Номер unknown, С. 169075 - 169075

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Resistance to Allosteric Inhibitors DOI
Ian R Outhwaite,

Isabelle Kwan,

Ariel Leyte-Vidal

и другие.

Journal of Molecular Biology, Год журнала: 2025, Номер unknown, С. 169133 - 169133

Опубликована: Апрель 1, 2025

Процитировано

0
In silico identification and experimental validation of long-range allosteric inhibition of Staphylococcus aureus Cas9 catalytic activity by an anti-CRISPR protein AcrIIA14 DOI
Jiacheng Wei,

Feiying Chen,

Xun Lu

и другие.

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 143324 - 143324

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Deciphering Allosteric Modulation of Cancer-Associated Histone Missense Mutations DOI Creative Commons
Shuxiang Li, Jie Shu,

James C. Rober

и другие.

Journal of Molecular Biology, Год журнала: 2025, Номер unknown, С. 169180 - 169180

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0