4HAB

Crystal structure of Plk1 Polo-box domain in complex with PL-49

Summary for 4HAB

• Entry DOI: 10.2210/pdb4hab/pdb
• Related PRD ID: PRD_000780
• Descriptor: Serine/threonine-protein kinase PLK1, PL-49, 3-CYCLOHEXYL-1-PROPYLSULFONIC ACID, ... (5 entities in total)
• Functional Keywords: polo-box domain, phosphoprotein-binding domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P53350
• Total number of polymer chains: 6
• Total formula weight: 81221.86

Authors

Lee, W.C.,Song, J.H.,Kim, H.Y. (deposition date: 2012-09-26, release date: 2013-04-03, Last modification date: 2022-12-21)

Primary citation

Murugan, R.N.,Park, J.E.,Lim, D.,Ahn, M.,Cheong, C.,Kwon, T.,Nam, K.Y.,Choi, S.H.,Kim, B.Y.,Yoon, D.Y.,Yaffe, M.B.,Yu, D.Y.,Lee, K.S.,Bang, J.K.
Development of cyclic peptomer inhibitors targeting the polo-box domain of polo-like kinase 1.
Bioorg.Med.Chem., 21:2623-2634, 2013

PubMed Abstract: The polo-box domain (PBD) of polo-like kinase 1 (Plk1) is essentially required for the function of Plk1 in cell proliferation. The availability of the phosphopeptide-binding pocket on PBD provides a unique opportunity to develop novel protein-protein interaction inhibitors. Recent identification of a minimal 5-residue-long phosphopeptide, PLHSpT, as a Plk1 PBD-specific ligand has led to the development of several peptide-based inhibitors, but none of them is cyclic peptide. Through the combination of single-peptoid mimics and thio-ether bridged cyclization, we successfully demonstrated for the first time two cyclic peptomers, PL-116 and PL-120, dramatically improved the binding affinity without losing mono-specificity against Plk1 PBD in comparison with the linear parental peptide, PLHSpT. These cyclic peptomers could serve as promising templates for future drug designs to inhibit Plk1 PBD.

PubMed: 23498919
DOI: 10.1016/j.bmc.2013.02.020

Experimental method

X-RAY DIFFRACTION (2.65 Å)