1 research outputs found
Structural Basis of Small-Molecule Aggregate Induced Inhibition of a Protein–Protein Interaction
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