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Identification of the target proteins for compound 1

ABSTRACT: In this project, we used biotin-labeled compound 1 to pull down proteins in U2OS cell lysates with or without the competition of free compound 1, and then to identify the cellular binding of compound 1.

ORGANISM(S): Homo Sapiens

SUBMITTER: Yanli Liu

PROVIDER: PXD034927 | iProX | Fri Jun 24 00:00:00 BST 2022

REPOSITORIES: iProX

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A small molecule antagonist of SMN disrupts the interaction between SMN and RNAP II.

Liu Yanli Y Iqbal Aman A Li Weiguo W Ni Zuyao Z Wang Yalong Y Ramprasad Jurupula J Abraham Karan Joshua KJ Zhang Mengmeng M Zhao Dorothy Yanling DY Qin Su S Loppnau Peter P Jiang Honglv H Guo Xinghua X Brown Peter J PJ Zhen Xuechu X Xu Guoqiang G Mekhail Karim K Ji Xingyue X Bedford Mark T MT Greenblatt Jack F JF Min Jinrong J

Nature communications 20220916 1

Survival of motor neuron (SMN) functions in diverse biological pathways via recognition of symmetric dimethylarginine (Rme2s) on proteins by its Tudor domain, and deficiency of SMN leads to spinal muscular atrophy. Here we report a potent and selective antagonist with a 4-iminopyridine scaffold targeting the Tudor domain of SMN. Our structural and mutagenesis studies indicate that both the aromatic ring and imino groups of compound 1 contribute to its selective binding to SMN. Various on-target ...[more]

PMID: 36114190

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