7DD1

Crystal structure of SRPK1 in complex with a peptide inhibitor

7DD1 の概要

• エントリーDOI: 10.2210/pdb7dd1/pdb
• 分子名称: SRSF protein kinase 1,SRSF protein kinase 1, ARG-GLU-ARG-ALA-ARG-THR-ARG (3 entities in total)
• 機能のキーワード: rna splicing, kinase inhibitor, peptide drug, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46270.08

構造登録者

Li, Q.Y.,Yung, K.W.Y.,Ngo, J.C.K. (登録日: 2020-10-27, 公開日: 2021-04-21, 最終更新日: 2023-11-29)

主引用文献

Li, Q.,Zeng, C.,Liu, H.,Yung, K.W.Y.,Chen, C.,Xie, Q.,Zhang, Y.,Wan, S.W.C.,Mak, B.S.W.,Xia, J.,Xiong, S.,Ngo, J.C.K.
Protein-Protein Interaction Inhibitor of SRPKs Alters the Splicing Isoforms of VEGF and Inhibits Angiogenesis.
Iscience, 24:102423-102423, 2021

PubMed Abstract: Serine-arginine (SR) protein kinases (SRPKs) regulate the functions of the SR-rich splicing factors by phosphorylating multiple serines within their C-terminal arginine-serine-rich domains. Dysregulation of these phosphorylation events has been implicated in many diseases, suggesting SRPKs are potential therapeutic targets. In particular, aberrant SRPK1 expression alters the balances of proangiogenic (VEGF) and antiangiogenic (VEGFb) splicing isoforms of the key angiogenesis factor, vascular endothelial growth factor (VEGF), through the phosphorylation of prototypic SR protein SRSF1. Here, we report a protein-protein interaction (PPI) inhibitor of SRPKs, docking blocker of SRPK1 (DBS1), that specifically blocks a conserved substrate docking groove unique to SRPKs. DBS1 is a cell-permeable inhibitor that effectively inhibits the binding and phosphorylation of SRSF1 and subsequently switches VEGF splicing from the proangiogenic to the antiangiogenic isoform. Our findings thus provide a new direction for the development of SRPK inhibitors through targeting a unique PPI site to combat angiogenic diseases.

PubMed: 33997701
DOI: 10.1016/j.isci.2021.102423

実験手法

X-RAY DIFFRACTION (2.05 Å)