• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

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.

DOI:10.4103/2277-9175.201683
PMID:28401073
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5359995/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5728/5359995/aef320b650ea/ABR-6-26-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5728/5359995/3decaab27d16/ABR-6-26-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5728/5359995/ff405cee8fc7/ABR-6-26-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5728/5359995/7116d0e86244/ABR-6-26-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5728/5359995/fd6f64125db4/ABR-6-26-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5728/5359995/754378c1161e/ABR-6-26-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5728/5359995/aef320b650ea/ABR-6-26-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5728/5359995/3decaab27d16/ABR-6-26-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5728/5359995/ff405cee8fc7/ABR-6-26-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5728/5359995/7116d0e86244/ABR-6-26-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5728/5359995/fd6f64125db4/ABR-6-26-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5728/5359995/754378c1161e/ABR-6-26-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5728/5359995/aef320b650ea/ABR-6-26-g007.jpg

相似文献

1
Structural Insight into Anaphase Promoting Complex 3 Structure and Docking with a Natural Inhibitory Compound.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
Adv Biomed Res. 2017 Mar 7;6:26. doi: 10.4103/2277-9175.201683. eCollection 2017.
2
TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1.后期促进复合物的TPR亚基介导与激活蛋白CDH1的结合。
Curr Biol. 2003 Sep 2;13(17):1459-68. doi: 10.1016/s0960-9822(03)00581-5.
3
Structure of an APC3-APC16 complex: insights into assembly of the anaphase-promoting complex/cyclosome.APC3-APC16复合物的结构：对后期促进复合物/细胞周期体组装的见解
J Mol Biol. 2015 Apr 24;427(8):1748-64. doi: 10.1016/j.jmb.2014.11.020. Epub 2014 Dec 6.
4
Cdc20 protein contains a destruction-box but, unlike Clb2, its proteolysisis not acutely dependent on the activity of anaphase-promoting complex.细胞分裂周期蛋白20（Cdc20）含有一个破坏框，但与周期蛋白B2（Clb2）不同，其蛋白水解并不严格依赖后期促进复合物的活性。
Eur J Biochem. 2000 Jan;267(2):434-49. doi: 10.1046/j.1432-1327.2000.01014.x.
5
A structural model of the anaphase promoting complex co-activator (Cdh1) and in silico design of inhibitory compounds.后期促进复合物共激活因子（Cdh1）的结构模型及抑制性化合物的计算机辅助设计
Res Pharm Sci. 2015 Jan-Feb;10(1):59-67.
6
The regulation of Cdc20 proteolysis reveals a role for APC components Cdc23 and Cdc27 during S phase and early mitosis.Cdc20蛋白水解的调控揭示了后期促进复合物组分Cdc23和Cdc27在S期和有丝分裂早期的作用。
Curr Biol. 1998 Jun 18;8(13):750-60. doi: 10.1016/s0960-9822(98)70298-2.
7
Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons.有丝分裂后神经元中促后期复合物的CDH1相关形式的表达。
Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11317-22. doi: 10.1073/pnas.96.20.11317.
8
The WD40 propeller domain of Cdh1 functions as a destruction box receptor for APC/C substrates.Cdh1的WD40螺旋桨结构域作为后期促进复合物/细胞周期体（APC/C）底物的破坏框受体发挥作用。
Mol Cell. 2005 May 27;18(5):543-53. doi: 10.1016/j.molcel.2005.04.023.
9
Molecular structure of the N-terminal domain of the APC/C subunit Cdc27 reveals a homo-dimeric tetratricopeptide repeat architecture.APC/C 亚基 Cdc27 的 N 端结构域的分子结构揭示了同源二聚体四肽重复结构。
J Mol Biol. 2010 Apr 16;397(5):1316-28. doi: 10.1016/j.jmb.2010.02.045. Epub 2010 Mar 3.
10
The Rae1-Nup98 complex prevents aneuploidy by inhibiting securin degradation.Rae1-Nup98复合物通过抑制分离酶降解来防止非整倍体的产生。
Nature. 2005 Dec 15;438(7070):1036-9. doi: 10.1038/nature04221.

引用本文的文献

1
Peptide inhibitors of the anaphase promoting-complex that cause sensitivity to microtubule poison.有丝分裂促进复合物的肽抑制剂可导致对微管毒物的敏感性。
PLoS One. 2018 Jun 8;13(6):e0198930. doi: 10.1371/journal.pone.0198930. eCollection 2018.

本文引用的文献

1
Mitochondrial dynamics, biogenesis, and function are coordinated with the cell cycle by APC/C CDH1.线粒体的动态、生物发生和功能通过 APC/C CDH1 与细胞周期相协调。
Cell Metab. 2012 Apr 4;15(4):466-79. doi: 10.1016/j.cmet.2012.03.003.
2
Emerging regulatory mechanisms in ubiquitin-dependent cell cycle control.泛素依赖性细胞周期调控中的新兴调控机制。
J Cell Sci. 2012 Jan 15;125(Pt 2):255-63. doi: 10.1242/jcs.091199.
3
Key role for ubiquitin protein modification in TGFβ signal transduction.泛素蛋白修饰在 TGFβ 信号转导中的关键作用。
Ups J Med Sci. 2012 May;117(2):153-65. doi: 10.3109/03009734.2012.654858. Epub 2012 Feb 15.
4
Substrate targeting by the ubiquitin-proteasome system in mitosis.有丝分裂中泛素-蛋白酶体系统的底物靶向。
Semin Cell Dev Biol. 2012 Jul;23(5):482-91. doi: 10.1016/j.semcdb.2012.01.015. Epub 2012 Jan 31.
5
Molecular basis for the association of microcephalin (MCPH1) protein with the cell division cycle protein 27 (Cdc27) subunit of the anaphase-promoting complex.微脑症蛋白 1（MCPH1）与细胞分裂周期蛋白 27（Cdc27）亚基形成复合物促进有丝分裂的分子基础。
J Biol Chem. 2012 Jan 20;287(4):2854-62. doi: 10.1074/jbc.M111.307868. Epub 2011 Dec 2.
6
LigPlot+: multiple ligand-protein interaction diagrams for drug discovery.LigPlot+：用于药物发现的多种配体-蛋白质相互作用图。
J Chem Inf Model. 2011 Oct 24;51(10):2778-86. doi: 10.1021/ci200227u. Epub 2011 Oct 5.
7
Meiotic control of the APC/C: similarities & differences from mitosis.有丝分裂期 APC/C 的调控：与减数分裂的异同。
Cell Div. 2011 Aug 1;6:16. doi: 10.1186/1747-1028-6-16.
8
Processive ubiquitin chain formation by the anaphase-promoting complex.后期促进复合物介导的连续泛素链形成。
Semin Cell Dev Biol. 2011 Aug;22(6):544-50. doi: 10.1016/j.semcdb.2011.03.009. Epub 2011 Apr 6.
9
How APC/C-Cdc20 changes its substrate specificity in mitosis.APC/C-Cdc20 在有丝分裂中如何改变其底物特异性。
Nat Cell Biol. 2011 Mar;13(3):223-33. doi: 10.1038/ncb2165. Epub 2011 Feb 20.
10
Structural basis for the subunit assembly of the anaphase-promoting complex.有丝分裂促进复合物亚基组装的结构基础。
Nature. 2011 Feb 10;470(7333):227-32. doi: 10.1038/nature09756.