后期促进复合物3结构及其与天然抑制性化合物对接的结构洞察
Structural Insight into Anaphase Promoting Complex 3 Structure and Docking with a Natural Inhibitory Compound.
作者信息
Rahimi Hamzeh, Shokrgozar Mohammad Ali, Madadkar-Sobhani Armin, Mahdian Reza, Foroumadi Alireza, Karimipoor Morteza
机构信息
Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran.
出版信息
Adv Biomed Res. 2017 Mar 7;6:26. doi: 10.4103/2277-9175.201683. eCollection 2017.
BACKGROUND
Anaphase promoting complex (APC) is the biggest Cullin-RING E3 ligase and is very important in cell cycle control; many anti-cancer agents target this. APC controls the onset of chromosome separation and mitotic exit through securin and cyclin B degradation, respectively. Its APC3 subunit identifies the APC activators-Cdh1 and Cdc20.
MATERIALS AND METHODS
The structural model of the APC3 subunit of APC was developed by means of computational techniques; the binding of a natural inhibitory compound to APC3 was also investigated.
RESULTS
It was found that APC3 structure consists of numerous helices organized in anti-parallel and the overall model is superhelical of tetratrico-peptide repeat (TPR) domains. Furthermore, binding pocket of the natural inhibitory compound as APC3 inhibitor was shown.
CONCLUSION
The findings are beneficial to understand the mechanism of the APC activation and design inhibitory compounds.
背景
后期促进复合物（APC）是最大的Cullin-RING E3连接酶，在细胞周期控制中非常重要；许多抗癌药物都靶向于此。APC分别通过降解securin和细胞周期蛋白B来控制染色体分离的开始和有丝分裂的退出。其APC3亚基识别APC激活剂——Cdh1和Cdc20。
材料与方法
通过计算技术建立了APC的APC3亚基的结构模型；还研究了一种天然抑制性化合物与APC3的结合。
结果
发现APC3结构由大量反平行排列的螺旋组成，整体模型是超螺旋的四三肽重复（TPR）结构域。此外，还展示了作为APC3抑制剂的天然抑制性化合物的结合口袋。
结论
这些发现有助于理解APC激活的机制并设计抑制性化合物。
Zotero 插件