logo
English (United Kingdom)Ukrainian (UA)
ABOUT News and Events A note of caution on the role of halogen bonds for protein kinase/inhibitor recognition suggested by high- and low-salt CK2α complex structures

A note of caution on the role of halogen bonds for protein kinase/inhibitor recognition suggested by high- and low-salt CK2α complex structures

Our paper in collaboration with Institute of Biochemistry, University of Cologne (Germany), dedicated to the investigation of cocrystal structures of protein kinase CK2 with inhibitor FLC26 has been published in ACS Chem. Biol. 

Abstract: CK2 is a Ser/Thr kinase recruited by tumor cells to avoid cell death. 4'-Carboxy-6,8-dibromo-flavonol (FLC26) is a nanomolar CK2 inhibitor reducing the physiological phosphorylation of CK2 biomarkers and inducing cell death. Ith binding mode to the ATP site was predicted to depend primarily on noncovalent interactions not comprising halogen bonds. We confirm this by two independent cocrystal structures which additionally show that FLC26 is selective for an open, protein kinase-untypical conformation of the hinge/helix αD region. The structures suggest how the bromo substituents, found previously in lead optimization studies, contribute to the inhibitory efficacy. In this context, one of the complex structures, obtained by crystallization with the kosmotropic salt NaCl, revealed an unconventional π-halogen bond between the 8-bromo substituent of FLC26 and an aromatic side chain which is absent under low-salt conditions. The kosmotropic salt sensitivity of π-halogen bonds is a novel feature which requires attention in structural comparisons and halogen-bond-based explanations.          

  • A note of caution on the role of halogen bonds for protein kinase/inhibitor recognition suggested by high- and low-salt CK2α complex structures. Guerra B, Bischoff N, Bdzhola VG, Yarmoluk SM, Issinger OG, Golub AG, Niefind K. ACS Chem Biol. 2015, 10(7):1654-1660.   

 

 

Our research:

CK2 Inhibitors
Aurone derivatives Image
Novel CK2 inhibitors among benzylidenebenzofuran-3(2H)-one (aurone) derivatives...



 

FGFR1 Inhibitors
N-phenylnaphthostyril-1-sulfonamides Image
New class of FGFR1 kinase inhibitors with naphthostyril heterocycle has been...



 

ASK1 Inhibitors

 

Molecular Design
Molecular Design Image
Molecular Design Laboratory of Medicinal Chemistry Department carry out...



 

Fluorescent Probes
Fluorescent dyes for study of beta-pleated protein formations Image
Uncontrolled proteins aggregation is considered to be the molecular basis for a...



 

© 2012 All rights reserved
footer logo