The Landscape of Atypical and Eukaryotic Protein Kinases

Department of Drug Design and Pharmacology

The Landscape of Atypical and Eukaryotic Protein Kinases

Research output: Contribution to journal › Review › Research › peer-review

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The Landscape of Atypical and Eukaryotic Protein Kinases. / Kanev, Georgi K; de Graaf, Chris; de Esch, Iwan J P; Leurs, Rob; Würdinger, Thomas; Westerman, Bart A; Kooistra, Albert J.

In: Trends in Pharmacological Sciences, Vol. 40, No. 11, 11.2019, p. 818-832.

Research output: Contribution to journal › Review › Research › peer-review

Harvard

Kanev, GK, de Graaf, C, de Esch, IJP, Leurs, R, Würdinger, T, Westerman, BA & Kooistra, AJ 2019, 'The Landscape of Atypical and Eukaryotic Protein Kinases', Trends in Pharmacological Sciences, vol. 40, no. 11, pp. 818-832. https://doi.org/10.1016/j.tips.2019.09.002

APA

Kanev, G. K., de Graaf, C., de Esch, I. J. P., Leurs, R., Würdinger, T., Westerman, B. A., & Kooistra, A. J. (2019). The Landscape of Atypical and Eukaryotic Protein Kinases. Trends in Pharmacological Sciences, 40(11), 818-832. https://doi.org/10.1016/j.tips.2019.09.002

Vancouver

Kanev GK, de Graaf C, de Esch IJP, Leurs R, Würdinger T, Westerman BA et al. The Landscape of Atypical and Eukaryotic Protein Kinases. Trends in Pharmacological Sciences. 2019 Nov;40(11):818-832. https://doi.org/10.1016/j.tips.2019.09.002

Author

Kanev, Georgi K ; de Graaf, Chris ; de Esch, Iwan J P ; Leurs, Rob ; Würdinger, Thomas ; Westerman, Bart A ; Kooistra, Albert J. / The Landscape of Atypical and Eukaryotic Protein Kinases. In: Trends in Pharmacological Sciences. 2019 ; Vol. 40, No. 11. pp. 818-832.

Bibtex

@article{c2a0d087ddbe46eea9d63d0a213c4edb,

title = "The Landscape of Atypical and Eukaryotic Protein Kinases",

abstract = "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.",

author = "Kanev, {Georgi K} and {de Graaf}, Chris and {de Esch}, {Iwan J P} and Rob Leurs and Thomas W{\"u}rdinger and Westerman, {Bart A} and Kooistra, {Albert J}",

year = "2019",

month = nov,

doi = "10.1016/j.tips.2019.09.002",

language = "English",

volume = "40",

pages = "818--832",

journal = "Trends in Pharmacological Sciences",

issn = "0165-6147",

publisher = "Elsevier Ltd. * Trends Journals",

number = "11",

}

RIS

TY - JOUR

T1 - The Landscape of Atypical and Eukaryotic Protein Kinases

AU - Kanev, Georgi K

AU - de Graaf, Chris

AU - de Esch, Iwan J P

AU - Leurs, Rob

AU - Würdinger, Thomas

AU - Westerman, Bart A

AU - Kooistra, Albert J

PY - 2019/11

Y1 - 2019/11

N2 - 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.

AB - 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.

U2 - 10.1016/j.tips.2019.09.002

DO - 10.1016/j.tips.2019.09.002

M3 - Review

C2 - 31677919

VL - 40

SP - 818

EP - 832

JO - Trends in Pharmacological Sciences

JF - Trends in Pharmacological Sciences

SN - 0165-6147

IS - 11

ER -

ID: 235972237