4RCP
Crystal structure of Plk1 Polo-box domain in complex with PL-2
Summary for 4RCP
| Entry DOI | 10.2210/pdb4rcp/pdb |
| Related PRD ID | PRD_001254 |
| Descriptor | Serine/threonine-protein kinase PLK1, PL-2, 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | polo-box domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus: P53350 |
| Total number of polymer chains | 2 |
| Total formula weight | 27628.45 |
| Authors | Lee, W.C.,Song, J.H.,Kim, H.Y. (deposition date: 2014-09-16, release date: 2014-11-12, Last modification date: 2024-10-16) |
| Primary citation | Ahn, M.,Han, Y.H.,Park, J.E.,Kim, S.,Lee, W.C.,Lee, S.J.,Gunasekaran, P.,Cheong, C.,Shin, S.Y.,Kim, H.Y.,Ryu, E.K.,Murugan, R.N.,Kim, N.H.,Bang, J.K. A new class of peptidomimetics targeting the polo-box domain of polo-like kinase 1. J.Med.Chem., 58:294-304, 2015 Cited by PubMed Abstract: Recent progress in the development of peptide-derived Polo-like kinase (Plk1) polo-box domain (PBD) inhibitors has led to the synthesis of multiple peptide ligands with high binding affinity and selectivity. However, few systematic analyses have been conducted to identify key Plk1 residues and characterize their interactions with potent Plk1 peptide inhibitors. We performed systematic deletion analysis using the most potent 4j peptide and studied N-terminal capping of the minimal peptide with diverse organic moieties, leading to the identification of the peptidomimetic 8 (AB-103) series with high binding affinity and selectivity. To evaluate the bioavailability of short peptidomimetic ligands, PEGylated 8 series were synthesized and incubated with HeLa cells to test for cellular uptake, antiproliferative activity, and Plk1 kinase inhibition. Finally, crystallographic studies of the Plk1 PBD in complex with peptidomimetics 8 and 22 (AB-103-5) revealed the presence of two hydrogen bond interactions responsible for their high binding affinity and selectivity. PubMed: 25347203DOI: 10.1021/jm501147g PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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