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.

中文翻译：

---

非典型和真核蛋白激酶的景观。

激酶由于其在肿瘤细胞的生长，存活和治疗抗性中的重要作用而成为有吸引力的抗癌靶标。这篇综述探讨了两种主要的激酶类别，即真核蛋白激酶（ePKs）和非典型蛋白激酶（aPKs），并提供了以结构为中心的序列，结构，疏水性棘突，突变和SNP热点以及抑制剂相互作用模式的比较。 。尽管这两个类别之间的序列相似性有限，但非典型激酶通常共享原型激酶折叠，但缺乏保守的真核激酶基序，并具有改变的疏水性刺。此外，非典型激酶抑制剂在正构结合位点内部和外部仅探索有限数量的结合模式。这两类中遗传变异的分布表明它们可以干扰激酶抑制剂结合的多种方式。这项多层综述提供了一个将真核和非典型激酶类别联系起来的研究框架。