5ZGG

NMR structure of p75NTR transmembrane domain in complex with NSC49652

Summary for 5ZGG

• Entry DOI: 10.2210/pdb5zgg/pdb
• NMR Information: BMRB: 36172
• Descriptor: Tumor necrosis factor receptor superfamily member 16, (2E)-1-(2-hydroxyphenyl)-3-(pyridin-3-yl)prop-2-en-1-one (2 entities in total)
• Functional Keywords: transmembrane, complex, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 7655.94

Authors

Lin, Z.,Ibanez, C. (deposition date: 2018-03-08, release date: 2019-03-13, Last modification date: 2024-11-13)

Primary citation

Goh, E.T.H.,Lin, Z.,Ahn, B.Y.,Lopes-Rodrigues, V.,Dang, N.H.,Salim, S.,Berger, B.,Dymock, B.,Senger, D.L.,Ibanez, C.F.
A Small Molecule Targeting the Transmembrane Domain of Death Receptor p75NTRInduces Melanoma Cell Death and Reduces Tumor Growth.
Cell Chem Biol, 25:1485-1494.e5, 2018

PubMed Abstract: Small molecules offer powerful ways to alter protein function. However, most proteins in the human proteome lack small-molecule probes, including the large class of non-catalytic transmembrane receptors, such as death receptors. We hypothesized that small molecules targeting the interfaces between transmembrane domains (TMDs) in receptor complexes may induce conformational changes that alter receptor function. Applying this concept in a screening assay, we identified a compound targeting the TMD of death receptor p75 that induced profound conformational changes and receptor activity. The compound triggered apoptotic cell death dependent on p75 and JNK activity in neurons and melanoma cells, and inhibited tumor growth in a melanoma mouse model. Due to their small size and crucial role in receptor activation, TMDs represent attractive targets for small-molecule manipulation of receptor function.

PubMed: 30293939
DOI: 10.1016/j.chembiol.2018.09.007

Experimental method

SOLUTION NMR