MyJournals Home  

RSS FeedsMolecules, Vol. 27, Pages 8282: Computer- and NMR-Aided Design of Small-Molecule Inhibitors of the Hub1 Protein (Molecules)

 
 

28 november 2022 10:03:03

 
Molecules, Vol. 27, Pages 8282: Computer- and NMR-Aided Design of Small-Molecule Inhibitors of the Hub1 Protein (Molecules)
 


By binding to the spliceosomal protein Snu66, the human ubiquitin-like protein Hub1 is a modulator of the spliceosome performance and facilitates alternative splicing. Small molecules that bind to Hub1 would be of interest to study the protein-protein interaction of Hub1/Snu66, which is linked to several human pathologies, such as hypercholesterolemia, premature aging, neurodegenerative diseases, and cancer. To identify small molecule ligands for Hub1, we used the interface analysis, peptide modeling of the Hub1/Snu66 interaction and the fragment-based NMR screening. Fragment-based NMR screening has not proven sufficient to unambiguously search for fragments that bind to the Hub1 protein. This was because the Snu66 binding pocket of Hub1 is occupied by pH-sensitive residues, making it difficult to distinguish between pH-induced NMR shifts and actual binding events. The NMR analyses were therefore verified experimentally by microscale thermophoresis and by NMR pH titration experiments. Our study found two small peptides that showed binding to Hub1. These peptides are the first small-molecule ligands reported to interact with the Hub1 protein.


 
49 viewsCategory: Biochemistry, Chemistry, Molecular Biology
 
Molecules, Vol. 27, Pages 8284: Design, Synthesis, Characterization, and Molluscicidal Activity Screening of New Nicotinonitrile Derivatives against Land Snails, M. cartusiana (Molecules)
Molecules, Vol. 27, Pages 8285: Physicochemical Properties and Functional Characteristics of Ecologically Extracted Shrimp Chitosans with Different Organic Acids during Demineralization Step (Molecules)
 
 
blog comments powered by Disqus


MyJournals.org
The latest issues of all your favorite science journals on one page

Username:
Password:

Register | Retrieve

Search:

Molecular Biology


Copyright © 2008 - 2023 Indigonet Services B.V.. Contact: Tim Hulsen. Read here our privacy notice.
Other websites of Indigonet Services B.V.: Nieuws Vacatures News Tweets Nachrichten