Kim, Dae Gyu; Huddar, Srigouri; Lim, Semi; Kong, Jiwon; Lee, Yuno; Park, Chul Min; Lee, Seungbeom; Suh, Young-Ger; Kim, Minkyoung; Lee, Kyeong; Lee, Sunkyung; Kim, Sunghoon published the artcile< Allosteric inhibition of the tumor-promoting interaction between exon 2-depleted splice variant of aminoacyl-transfer RNA synthetase-interacting multifunctional protein 2 and heat shock protein 70>, Reference of 94-02-0, the main research area is aminoacyl tRNA synthetase heat shock protein allosteric inhibition.
Although protein-protein interactions (PPIs) have emerged as an attractive therapeutic target space, the identification of chems. that effectively inhibit PPIs remains challenging. Here, we identified through library screening a chem. probe (compound 1) that can inhibit the tumor-promoting interaction between the oncogenic factor exon 2-depleted splice variant of aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2-DX2) and heat shock protein 70 (HSP70). We found that compound 1 binds to the N-terminal subdomain of glutathione S-transferase (GST-N) of AIMP2-DX2, causing a direct steric clash with HSP70 and an intramol. interaction between the N-terminal flexible region and the GST-N of AIMP2-DX2, which induces masking of the HSP70 binding region during mol. dynamics and mutation studies. Compound 1 thus interferes with the AIMP2-DX2 and HSP70 interaction and suppresses the growth of cancer cells that express high levels of AIMP2-DX2 in vitro and in preliminary in vivo experiment This work provides an example showing that allosteric conformational changes induced by chems. can be a way to control pathol. PPIs.
Journal of Pharmacology and Experimental Therapeutics published new progress about Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 94-02-0 belongs to class esters-buliding-blocks, and the molecular formula is C11H12O3, Reference of 94-02-0.
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