2LK1

Solution structure and binding studies of the RanBP2-type zinc finger of RBM5

2LK1 の概要

• エントリーDOI: 10.2210/pdb2lk1/pdb
• 関連するPDBエントリー: 2LK1
• NMR情報: BMRB: 17970
• 分子名称: RNA-binding protein 5, 9,10-dioxo-9,10-dihydroanthracene-2-sulfonic acid, ZINC ION (3 entities in total)
• 機能のキーワード: zinc finger, rna binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P52756
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4088.13

構造登録者

Farina, B.,Pellecchia, M. (登録日: 2011-09-30, 公開日: 2011-12-28, 最終更新日: 2024-11-27)

主引用文献

Farina, B.,Fattorusso, R.,Pellecchia, M.
Targeting Zinc Finger Domains with Small Molecules: Solution Structure and Binding Studies of the RanBP2-Type Zinc Finger of RBM5.
Chembiochem, 12:2837-2845, 2011

PubMed Abstract: The RNA binding motif protein 5 (RBM5), also known as Luca15 or H37, is a component of prespliceosomal complexes that regulates the alternative splicing of several mRNAs, such as Fas and caspase-2. The RBM5 gene is located at the 2p21.3 chromosomal region, which is strongly associated with lung cancer and many other cancers. Both increased and decreased levels of RBM5 can play a role in tumor progression. In particular, downregulation of rbm5 is involved in lung cancer and other cancers upon Ras activation, and, also, represents a molecular signature associated with metastasis in various solid tumors. On the other hand, upregulation of RBM5 occurs in breast and ovarian cancer. Moreover, RBM5 was also found to be involved in the early stage of the HIV-1 viral cycle, representing a potential target for the treatment of the HIV-1 infection. While the molecular basis for RNA recognition and ubiquitin interaction has been structurally characterized, small molecules binding this zinc finger (ZF) domain that might contribute to characterizing their activity and to the development of potential therapeutic agents have not yet been reported. Using an NMR screening of a fragment library we identified several binders and the complex of the most promising one, compound 1, with the RBM5 ZF1 was structurally characterized in solution. Interestingly, the binding mechanism reveals that 1 occupies the RNA binding pocket and is therefore able to compete with the RNA to bind RBM5 RanBP2-type ZF domain, as indicated by NMR studies.

PubMed: 22162216
DOI: 10.1002/cbic.201100582

実験手法

SOLUTION NMR