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5ORK

The crystal structure of CK2alpha in complex with compound 6

Summary for 5ORK
Entry DOI10.2210/pdb5ork/pdb
DescriptorCasein kinase II subunit alpha, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (7 entities in total)
Functional Keywordsck2alpha, ck2a, fragment based drug discovery, high concentration screening, selective atp competitive inhibitors, surface entrophy reduction, transferase
Biological sourceHomo sapiens (Human)
Cellular locationNucleus : P68400
Total number of polymer chains2
Total formula weight84204.71
Authors
Brear, P.,De Fusco, C.,Iegre, J.,Yoshida, M.,Mitchell, S.,Rossmann, M.,Carro, L.,Sore, H.,Hyvonen, M.,Spring, D. (deposition date: 2017-08-16, release date: 2018-02-28, Last modification date: 2024-01-17)
Primary citationIegre, J.,Brear, P.,De Fusco, C.,Yoshida, M.,Mitchell, S.L.,Rossmann, M.,Carro, L.,Sore, H.F.,Hyvonen, M.,Spring, D.R.
Second-generation CK2 alpha inhibitors targeting the alpha D pocket.
Chem Sci, 9:3041-3049, 2018
Cited by
PubMed Abstract: CK2 is a critical cell cycle regulator that also promotes various anti-apoptotic mechanisms. Development of ATP-non-competitive inhibitors of CK2 is a very attractive strategy considering that the ATP binding site is highly conserved among other kinases. We have previously utilised a pocket outside the active site to develop a novel CK2 inhibitor, . Whilst bound to this new pocket it was also interacting with the ATP site: herein, we describe an example of a CK2α inhibitor that binds completely outside the active site. This second generation αD-site binding inhibitor, compound (IC = 7 μM, GI = 10.0 ± 3.6 μM), has numerous advantages over the previously reported , including a reduction in the number of rotatable bonds, the absence of amide groups susceptible to the action of proteases and improved cellular permeability. Unlike with , there was no need to facilitate cellular uptake by making a prodrug. Moreover, displayed no drop off between its ability to inhibit the kinase (IC) and the ability to inhibit cell proliferation (GI).
PubMed: 29732088
DOI: 10.1039/c7sc05122k
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.143 Å)
Structure validation

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數據於2024-11-06公開中

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