聚（ADP - 核糖）聚合酶家族蛋白中烟酰胺结合位点的生物信息学分析
Bioinformatic Analysis of the Nicotinamide Binding Site in Poly(ADP-Ribose) Polymerase Family Proteins.
作者信息
Manasaryan Garri, Suplatov Dmitry, Pushkarev Sergey, Drobot Viktor, Kuimov Alexander, Švedas Vytas, Nilov Dmitry
机构信息
Faculty of Medicine, Lomonosov Moscow State University, Lomonosov Ave. 27, bldg. 1, 119991 Moscow, Russia.
Belozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, Lenin Hills 1, bldg. 40, 119991 Moscow, Russia.
出版信息
Cancers (Basel). 2021 Mar 10;13(6):1201. doi: 10.3390/cancers13061201.
The PARP family consists of 17 members with diverse functions, including those related to cancer cells' viability. Several PARP inhibitors are of great interest as innovative anticancer drugs, but they have low selectivity towards distinct PARP family members and exert serious adverse effects. We describe a family-wide study of the nicotinamide (NA) binding site, an important functional region in the PARP structure, using comparative bioinformatic analysis and molecular modeling. Mutations in the NA site and D-loop mobility around the NA site were identified as factors that can guide the design of selective PARP inhibitors. Our findings are of particular importance for the development of novel tankyrase (PARPs 5a and 5b) inhibitors for cancer therapy.
PARP家族由17个具有不同功能的成员组成，包括与癌细胞生存能力相关的功能。几种PARP抑制剂作为创新的抗癌药物备受关注，但它们对不同PARP家族成员的选择性较低，并会产生严重的副作用。我们通过比较生物信息学分析和分子建模，对PARP结构中的一个重要功能区域——烟酰胺（NA）结合位点进行了全家族研究。NA位点的突变以及NA位点周围D环的流动性被确定为可指导选择性PARP抑制剂设计的因素。我们的研究结果对于开发用于癌症治疗的新型端锚聚合酶（PARPs 5a和5b）抑制剂尤为重要。
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