Universität zu Köln

Niefind, Karsten ORCID: 0000-0002-0183-6315, Bischoff, Nils, Golub, Andriy G., Bdzhola, Volodymyr G., Balanda, Anatoliy O., Prykhod'ko, Andriy O. and Yarmoluk, Sergiy M. (2017). Structural Hypervariability of the Two Human Protein Kinase CK2 Catalytic Subunit Paralogs Revealed by Complex Structures with a Flavonol- and a Thieno[2,3-d]pyrimidine-Based Inhibitor. Pharmaceuticals, 10 (1). BASEL: MDPI. ISSN 1424-8247

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Abstract

Protein kinase CK2 is associated with a number of human diseases, among them cancer, and is therefore a target for inhibitor development in industry and academia. Six crystal structures of either CK2 alpha, the catalytic subunit of human protein kinase CK2, or its paralog CK2 alpha' in complex with two ATP-competitive inhibitors-based on either a flavonol or a thieno[2,3-d]pyrimidine framework-are presented. The structures show examples for extreme structural deformations of the ATP-binding loop and its neighbourhood and of the hinge/helix alpha D region, i.e., of two zones of the broader ATP site environment. Thus, they supplement our picture of the conformational space available for CK2 alpha and CK2 alpha'. Further, they document the potential of synthetic ligands to trap unusual conformations of the enzymes and allow to envision a new generation of inhibitors that stabilize such conformations.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Niefind, Karsten UNSPECIFIED orcid.org/0000-0002-0183-6315 UNSPECIFIED Bischoff, Nils UNSPECIFIED UNSPECIFIED UNSPECIFIED Golub, Andriy G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bdzhola, Volodymyr G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Balanda, Anatoliy O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Prykhod'ko, Andriy O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Yarmoluk, Sergiy M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-236958
DOI:	10.3390/ph10010009
Journal or Publication Title:	Pharmaceuticals
Volume:	10
Number:	1
Date:	2017
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1424-8247
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CRYSTAL-STRUCTURE; CONFORMATIONAL PLASTICITY; HUMAN CK2-ALPHA; MAP KINASE; BINDING; SURVIVAL; CX-4945; TOOL; ABL; ATP Multiple languages Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23695