4DFW

Oxime-based Post Solid-phase Peptide Diversification: Identification of High Affinity Polo-like Kinase 1 (Plk1) Polo-box Domain Binding Peptides

Summary for 4DFW

• Entry DOI: 10.2210/pdb4dfw/pdb
• Descriptor: Serine/threonine-protein kinase PLK1, Peptide, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: phospho binding domain, transcription-antagonist complex, transcription/antagonist
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P53350
• Total number of polymer chains: 2
• Total formula weight: 28149.86

Authors

Liu, F.,Park, J.-E.,Qian, W.-J.,Lim, D.,Gr ber, M.,Berg, T.,Yaffe, M.B.,Lee, K.S.,Burke Jr., T.R. (deposition date: 2012-01-24, release date: 2012-03-28, Last modification date: 2023-11-15)

Primary citation

Liu, F.,Park, J.-E.,Qian, W.-J.,Lim, D.,Scharow, A.,Berg, T.,Yaffe, M.B.,Lee, K.S.,Burke, T.R.
Oxime-based Post Solid-phase Peptide Diversification: Identification of High Affinity Polo-like Kinase 1 (Plk1) Polo-box Domain Binding Peptides
Chem.Biol., 2012

PubMed Abstract: In an effort to develop improved binding antagonists of the polo-like kinase 1 (Plk1) polo-box domain (PBD), we optimized interactions of the known high affinity 5-mer peptide PLHSpT using oxime-based post solid-phase peptide diversification of the N-terminal Pro residue. This allowed us to achieve up to two orders of magnitude potency enhancement. An X-ray crystal structure of the highest affinity analogue in complex with Plk1 PBD revealed new binding interactions in a hydrophobic channel that had been occluded in X-ray structures of the unliganded protein. This study represents an important example where amino acid modification by post solid-phase oxime ligation can facilitate the development of protein-protein interaction inhibitors by identifying new binding pockets that would not otherwise be accessible to coded amino acid residues.

PubMed: 22292814

Experimental method

X-RAY DIFFRACTION (1.55 Å)