6Q38

The Crystal structure of CK2a bound to P1-C4

This is a non-PDB format compatible entry.

Summary for 6Q38

• Entry DOI: 10.2210/pdb6q38/pdb
• Related PRD ID: PRD_002559
• Descriptor: Casein kinase II subunit alpha, Stapled Peptide, BENZOIC ACID, ... (5 entities in total)
• Functional Keywords: ck2alpha, ck2a, stapled peptides, high concentration screening, selective atp competitive inhibitors, surface entrophy reduction, peptide binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 40870.57

Authors

Brear, P.,Iegre, J.,Baker, D.,Tan, Y.,Sore, H.,Donovan, D.,Spring, D.,Chandra, V.,Hyvonen, M. (deposition date: 2018-12-03, release date: 2019-04-24, Last modification date: 2024-11-13)

Primary citation

Iegre, J.,Brear, P.,Baker, D.J.,Tan, Y.S.,Atkinson, E.L.,Sore, H.F.,O' Donovan, D.H.,Verma, C.S.,Hyvonen, M.,Spring, D.R.
Efficient development of stable and highly functionalised peptides targeting the CK2 alpha /CK2 beta protein-protein interaction.
Chem Sci, 10:5056-5063, 2019

PubMed Abstract: The discovery of new Protein-Protein Interaction (PPI) modulators is currently limited by the difficulties associated with the design and synthesis of selective small molecule inhibitors. Peptides are a potential solution for disrupting PPIs; however, they typically suffer from poor stability and limited tissue penetration hampering their wide spread use as new chemical biology tools and potential therapeutics. In this work, a combination of CuAAC chemistry, molecular modelling, X-ray crystallography, and biological validation allowed us to develop highly functionalised peptide PPI inhibitors of the protein CK2. The lead peptide, , prevents the formation of the holoenzyme assembly , slows down proliferation, induces apoptosis in cancer cells and is stable in human serum. could aid the development of novel CK2 inhibitors acting at the interface and help to fully understand the intracellular pathways involving CK2. Importantly, the approach adopted herein could be applied to many PPI targets and has the potential to ease the study of PPIs by efficiently providing access to functionalised peptides.

PubMed: 31183056
DOI: 10.1039/c9sc00798a

Experimental method

X-RAY DIFFRACTION (1.74 Å)