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

James C. Rober

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169180 - 169180

Published: April 1, 2025

Language: 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

et al.

Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

Citations

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

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169050 - 169050

Published: Feb. 1, 2025

Language: Английский

Citations

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

E. Srinivasan,

Grigor Arakelov, Nikolay V. Dokholyan

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169060 - 169060

Published: March 1, 2025

Language: Английский

Citations

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

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169075 - 169075

Published: March 1, 2025

Language: Английский

Citations

0
Resistance to Allosteric Inhibitors DOI
Ian R Outhwaite,

Isabelle Kwan,

Ariel Leyte-Vidal

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169133 - 169133

Published: April 1, 2025

Citations

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

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 143324 - 143324

Published: April 1, 2025

Language: Английский

Citations

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

James C. Rober

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169180 - 169180

Published: April 1, 2025

Language: Английский

Citations

0