7DD1
Crystal structure of SRPK1 in complex with a peptide inhibitor
Summary for 7DD1
| Entry DOI | 10.2210/pdb7dd1/pdb |
| Descriptor | SRSF protein kinase 1,SRSF protein kinase 1, ARG-GLU-ARG-ALA-ARG-THR-ARG (3 entities in total) |
| Functional Keywords | rna splicing, kinase inhibitor, peptide drug, transferase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 46270.08 |
| Authors | Li, Q.Y.,Yung, K.W.Y.,Ngo, J.C.K. (deposition date: 2020-10-27, release date: 2021-04-21, Last modification date: 2023-11-29) |
| Primary citation | 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 Cited by 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: 33997701DOI: 10.1016/j.isci.2021.102423 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
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