Leibly David J, Newling Paul A, Abendroth Jan, Guo Wenjin, Kelley Angela, Stewart Lance J, Van Voorhis Wesley
Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Sep 1;67(Pt 9):1084-9. doi: 10.1107/S1744309111018070. Epub 2011 Aug 16.
Giardia lamblia is the etiologic agent of giardiasis, a water-borne infection that is prevalent throughout the world. The need for new therapeutics for the treatment of giardiasis is of paramount importance. Owing to the ubiquitous nature of kinases and their vital importance in organisms, they are potential drug targets. In this paper, the first structure of a cyclin-dependent kinase (CDK) from G. lamblia (GlCDK; UniProt A8BZ95) is presented. CDKs are cell-cycle-associated kinases that are actively being pursued as targets for anticancer drugs as well as for antiparasitic chemotherapy. Generally, a CDK forms a complex with its associated cyclin. This CDK-cyclin complex is active and acts as a serine/threonine protein kinase. Typically, CDKs are responsible for the transition to the next phase of the cell cycle. Although the structure of GlCDK with its associated cyclin was not solved, the 1.85 Å resolution structure of apo GlCDK and a 2.0 Å resolution structure of GlCDK in complex with adenosine monophosphate are presented and the structural differences from the orthologous human CDK2 and CDK3 are discussed.
蓝氏贾第鞭毛虫是贾第虫病的病原体，这是一种通过水传播的感染病，在全球范围内普遍存在。开发治疗贾第虫病的新疗法至关重要。由于激酶在生物体内普遍存在且至关重要，它们是潜在的药物靶点。本文展示了蓝氏贾第鞭毛虫细胞周期蛋白依赖性激酶（CDK；UniProt A8BZ95）的首个结构。CDK是与细胞周期相关的激酶，目前正被积极研究作为抗癌药物以及抗寄生虫化疗的靶点。一般来说，CDK与其相关的细胞周期蛋白形成复合物。这种CDK - 细胞周期蛋白复合物具有活性，并作为丝氨酸/苏氨酸蛋白激酶发挥作用。通常，CDK负责细胞周期向下一阶段的转变。尽管未解析出GlCDK与其相关细胞周期蛋白的结构，但展示了apo GlCDK的1.85 Å分辨率结构以及与单磷酸腺苷结合的GlCDK的2.0 Å分辨率结构，并讨论了与直系同源人类CDK2和CDK3的结构差异。
