9IM7
Crystal structure of mouse Plk1-PBD in complex with R12-4j compound
This is a non-PDB format compatible entry.
Summary for 9IM7
| Entry DOI | 10.2210/pdb9im7/pdb |
| Descriptor | Serine/threonine-protein kinase PLK1, (ACE)(A1L2U)L(56A)S(YTH)(NH2) (3 entities in total) |
| Functional Keywords | plk1 pbd, complex, inhibitor, transferase |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 2 |
| Total formula weight | 26815.57 |
| Authors | |
| Primary citation | Gunasekaran, P.,Shin, S.C.,Hwang, Y.S.,Lee, J.,La, Y.K.,Yim, M.S.,Kim, H.N.,Kim, T.W.,Yang, E.,Lee, S.J.,Yoon, J.M.,Kim, E.E.,Jeon, S.,Ryu, E.K.,Bang, J.K. N-Degron-Based PROTAC Targeting PLK1: A Potential Therapeutic Strategy for Cervical Cancer. Pharmaceutics, 17:-, 2025 Cited by PubMed Abstract: : Cervical cancer remains a major global health concern, with existing chemotherapy facing limited effectiveness owing to resistance. Polo-like kinase 1 (PLK1) overexpression in cervical cancer cells is a promising target for developing novel therapies to overcome chemoresistance and improve treatment efficacy. : In this study, we developed a novel PROTAC, NC1, targeting PLK1 PBD via the N-end rule pathway. : This PROTAC effectively depleted the PLK1 protein in HeLa cells by inducing protein degradation. The crystal structure of the PBD-NC1 complex identified key PLK1 PBD binding interactions and isothermal titration calorimetry (ITC) confirmed a binding affinity of 6.06 µM between NC1 and PLK1 PBD. NC1 significantly decreased cell viability with an IC of 5.23 µM, induced G2/M phase arrest, and triggered apoptosis in HeLa cells. In vivo, NC1 suppressed tumor growth in a HeLa xenograft mouse model. : This research highlights the potential of N-degron-based PROTACs targeting the PLK1 protein in cancer therapies, highlighting their potential in future cervical anticancer treatment strategies. PubMed: 40871048DOI: 10.3390/pharmaceutics17081027 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.93 Å) |
Structure validation
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