| Literature DB >> 28300404 |
Jonathan M Blevitt1, Michael D Hack2, Krystal L Herman1, Paul F Jackson1, Paul J Krawczuk3, Alec D Lebsack4, Annie X Liu5, Taraneh Mirzadegan2, Marina I Nelen6, Aaron N Patrick5, Stefan Steinbacher7, Marcos E Milla1, Kevin J Lumb5.
Abstract
A prevalent observation in high-throughput screening and drug discovery programs is the inhibition of protein function by small-molecule compound aggregation. Here, we present the X-ray structural description of aggregation-based inhibition of a protein-protein interaction involving tumor necrosis factor α (TNFα). An ordered conglomerate of an aggregating small-molecule inhibitor (JNJ525) induces a quaternary structure switch of TNFα that inhibits the protein-protein interaction between TNFα and TNFα receptors. SPD-304 may employ a similar mechanism of inhibition.Entities:
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Year: 2017 PMID： 28300404 DOI： 10.1021/acs.jmedchem.6b01836
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446