5MU8

HUMAN TNF-ALPHA IN COMPLEX WITH JNJ525

Summary for 5MU8

• Entry DOI: 10.2210/pdb5mu8/pdb
• Descriptor: Tumor necrosis factor, ~{N}4-(phenylmethyl)-~{N}4-[2-[3-(2-piperazin-1-ylpyrimidin-5-yl)phenyl]phenyl]pyrimidine-2,4-diamine (2 entities in total)
• Functional Keywords: tumor necrosis factor alpha, proteros biostructures gmbh, cytokine
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 48
• Total formula weight: 867173.44

Authors

Blevitt, J.M.,Hack, M.D.,Herman, K.L.,Jackson, P.F.,Krawczuk, P.J.,Lebsack, A.D.,Liu, A.X.,Mirzadegan, T.,Nelen, M.I.,Patrick, A.P.,Steinbacher, S.,Milla, M.E.,Lumb, K.J. (deposition date: 2017-01-12, release date: 2017-03-29, Last modification date: 2024-11-13)

Primary citation

Blevitt, J.M.,Hack, M.D.,Herman, K.L.,Jackson, P.F.,Krawczuk, P.J.,Lebsack, A.D.,Liu, A.X.,Mirzadegan, T.,Nelen, M.I.,Patrick, A.N.,Steinbacher, S.,Milla, M.E.,Lumb, K.J.
Structural Basis of Small-Molecule Aggregate Induced Inhibition of a Protein-Protein Interaction.
J. Med. Chem., 60:3511-3517, 2017

PubMed 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.

PubMed: 28300404
DOI: 10.1021/acs.jmedchem.6b01836

Experimental method

X-RAY DIFFRACTION (3 Å)