泛酸激酶的克隆鉴定及其与泛酸类似物的作用

Cloning and confirmation of several potential pantothenate kinases and their interaction with pantothenate analogues

泛酸激酶在生物体代谢过程中起重要作用,且在进化上高度分化。为验证或支持泛酸激酶是潜在的药物靶点这个观点,研究克隆了5种物种中可能的泛酸激酶基因,验证其编码的蛋白能与大肠杆菌缺陷的泛酸激酶功能互补。同时在大肠杆菌模型中检测了其中4种泛酸激酶被6种泛酸类似物特异性抑制的情况,所得结果与体内实验一致。研究表明:泛酸激酶可作为药物研发的靶点,并提出了高通量筛选泛酸激酶靶向药物的可能性。

Pantothenate kinase （PanK）, which evolved quickly during evolution, plays an important role in metabolic pathways. PanKs may be potential drug targets to inhibit the growth of certain organisms. In this study, PanK candidate genes from several organisms were cloned, and their PanK activities were demonstrated in an E. coli model, The specificity of four PanKs towards six known or possible antimetabolites was also analyzed. The E. coli results were consistent with results from in vivo cell growth inhibitory experiments. The studies lend further support to the notion that PanKs are potential targets for drug development and suggest the possibility of using high throughput screening for compounds that specifically interact with individual PanKs.