6HNW

Inhibitory Properties of ATP-Competitive Coumestrol and Boldine Are Correlated to Different Modulations of CK2 Flexibility.

(2019) J Nat Prod 82: 1014-1018

• PubMed: 30840451 Search on PubMed
• DOI: https://doi.org/10.1021/acs.jnatprod.8b00889
• Primary Citation of Related Structures:  
  6HNW, 6HNY


• PubMed Abstract: 
  

  Casein kinase 2 (CK2) is an anti-apoptotic cancer-sustaining protein kinase. Its crystallographic structures with the natural compounds coumestrol, a phytoestrogen, and boldine, an alkaloid, are reported. Coumestrol shows different inhibitory activity against the isolated catalytic α-subunit and the α ₂ β ₂ holoenzyme and is able to discriminate between two conformations of the hinge/αD region, whose intrinsic flexibility is a relevant selectivity determinant among kinases. Boldine explores a small cavity at the bottom of the ATP-binding pocket through a local deviation from planarity, a unique case among CK2 inhibitors. The two compounds have different impacts on protein flexibility, which correlate with their different properties.

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Organizational Affiliation: 

Department of Chemical Sciences , University of Padua and Institute of Biomolecular Chemistry, National Research Council (CNR) , 35131 Padua , Italy.