The Landscape of Atypical and Eukaryotic Protein Kinases

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Kinases are attractive anticancer targets due to their central role in the growth, survival, and therapy resistance of tumor cells. This review explores the two primary kinase classes, the eukaryotic protein kinases (ePKs) and the atypical protein kinases (aPKs), and provides a structure-centered comparison of their sequences, structures, hydrophobic spines, mutation and SNP hotspots, and inhibitor interaction patterns. Despite the limited sequence similarity between these two classes, atypical kinases commonly share the archetypical kinase fold but lack conserved eukaryotic kinase motifs and possess altered hydrophobic spines. Furthermore, atypical kinase inhibitors explore only a limited number of binding modes both inside and outside the orthosteric binding site. The distribution of genetic variations in both classes shows multiple ways they can interfere with kinase inhibitor binding. This multilayered review provides a research framework bridging the eukaryotic and atypical kinase classes.

Original languageEnglish
JournalTrends in Pharmacological Sciences
Issue number11
Pages (from-to)818-832
Number of pages15
Publication statusPublished - Nov 2019
Externally publishedYes

Bibliographical note

Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

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