The Landscape of Atypical and Eukaryotic Protein Kinases.

Autor: Kanev GK; Division of Medicinal Chemistry, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands; Department of Neurosurgery, Amsterdam University Medical Centers, Cancer Center Amsterdam, Brain Tumor Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands., de Graaf C; Division of Medicinal Chemistry, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands., de Esch IJP; Division of Medicinal Chemistry, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands., Leurs R; Division of Medicinal Chemistry, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands., Würdinger T; Department of Neurosurgery, Amsterdam University Medical Centers, Cancer Center Amsterdam, Brain Tumor Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands., Westerman BA; Department of Neurosurgery, Amsterdam University Medical Centers, Cancer Center Amsterdam, Brain Tumor Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Electronic address: a.westerman@amsterdamumc.nl., Kooistra AJ; Division of Medicinal Chemistry, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands. Electronic address: albert.kooistra@sund.ku.dk.
Jazyk: angličtina
Zdroj: Trends in pharmacological sciences [Trends Pharmacol Sci] 2019 Nov; Vol. 40 (11), pp. 818-832. Date of Electronic Publication: 2019 Oct 31.
DOI: 10.1016/j.tips.2019.09.002
Abstrakt: 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.
(Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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