A structural model of the anaphase promoting complex co-activator (Cdh1) and in silico design of inhibitory compounds

被引：0

作者：

Rahimi, H. ^{[1
]}

Negandari, B. ^{[2
]}

Shokrgozar, M. A. ^{[3
]}

Madadkar-Sobhani, A. ^{[4
,5
]}

Mahdian, R. ^{[1
]}

Foroumadi, A. ^{[6
,7
]}

Amin, M. Kafshdouzi ^{[8
]}

Karimipoor, M. ^{[1
]}

机构：

[1] Pasteur Inst Iran, Biotechnol Res Ctr, Dept Mol Med, Tehran, Iran

[2] Univ Tehran Med Sci, Adv Med Sci Sch, Dept Med Biotechnol, Tehran, Iran

[3] Pasteur Inst Iran, Natl Cell Bank Iran, Tehran, Iran

[4] Barcelona Supercomputing Ctr, Dept Life Sci, Barcelona 08034, Spain

[5] Univ Tehran, Inst Biochem & Biophys, Dept Bioinformat, Tehran, Iran

[6] Univ Tehran Med Sci, Fac Pharm, Tehran, Iran

[7] Univ Tehran Med Sci, Pharmaceut Sci Res Ctr, Tehran, Iran

[8] Qazvin Univ Med Sci, Fac Paramed Sci, Qazvin, Iran

来源：

RESEARCH IN PHARMACEUTICAL SCIENCES | 2015年 / 10卷 / 01期

关键词：

Cdh1; Cancer; Homology modeling; Virtual screening and docking;

D O I：

暂无

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Anaphase promoting complex (APC) controls cell cycle and chromosome segregation. The APC activation occurs after binding of co-activators, cdh1 and cdc20. Cdh1 plays a role in cancer pathogenesis and is known as a potential drug target. The main aim of this study was prediction of 3D structure of cdh1 and designing the inhibitory compounds based on the structural model. First, 3D structure of cdh1 was predicted by means of homology modelling and molecular dynamics tools, MODELLER and Gromacs package, respectively. Then, inhibitory compounds were designed using virtual screening and molecular docking by means AutoDock package. The overall structure of cdh1 is propeller like and each DW (40) repeat contains four anti-parallel beta-sheets. Moreover, binding pocket of the inhibitory compounds was determined. The results might be helpful in finding a suitable cdh1 inhibitor for the treatment of cancer.

引用

页码：59 / 67

页数：9

共 48 条

[1] Ashari A, 2012, RES PHARM SCI, V7, pS579
[2] Substrate binding on the APC/C occurs between the coactivator Cdh1 and the processivity factor Doc1
Buschhorn, Bettina A.
Petzold, Georg
Galova, Marta
Dube, Prakash
Kraft, Claudine
Herzog, Franz
Stark, Holger
Peters, Jan-Michael
[J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2011, 18 (01) : 6 - +
[3] Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma differentiation and progression
Chang, David Z.
Ma, Ying
Ji, Baoan
Liu, Yan
Hwu, Patrick
Abbruzzese, James L.
Logsdon, Craig
Wang, Huamin
[J]. JOURNAL OF HEMATOLOGY & ONCOLOGY, 2012, 5
[4] The Anaphase-Promoting Complex or Cyclosome Supports Cell Survival in Response to Endoplasmic Reticulum Stress
Chen, Meifan
Gutierrez, Gustavo J.
Ronai, Ze'ev A.
[J]. PLOS ONE, 2012, 7 (04):
[5] The spindle checkpoint, APC/CCdc20, and APC/CCdh1 play distinct roles in connecting mitosis to S phase
Clijsters, Linda
Ogink, Janneke
Wolthuis, Rob
[J]. JOURNAL OF CELL BIOLOGY, 2013, 201 (07) : 1013 - 1026
[6] Localization of the coactivator Cdh1 and the cullin subunit Apc2 in a cryo-electron microscopy model of vertebrate APC/C
Dube, P
Herzog, F
Gieffers, C
Sander, B
Riedel, D
Müller, SA
Engel, A
Peters, JM
Stark, H
[J]. MOLECULAR CELL, 2005, 20 (06) : 867 - 879
[7] Non-mitotic functions of the Anaphase-Promoting Complex
Eguren, Manuel
Manchado, Eusebio
Malumbres, Marcos
[J]. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2011, 22 (06) : 572 - 578
[8] Eswar Narayanan, 2008, V426, P145, DOI 10.1007/978-1-60327-058-8_8
[9] Webb Benjamin, 2016, Curr Protoc Protein Sci, V86, DOI [10.1002/0471250953.bi0506s15, 10.1002/cpbi.3, 10.1002/0471140864.ps0209s50, 10.1002/cpps.20]
[10] Dissection of the ApCCdh1-Skp2 cascade in breast cancer
Fujita, Takeo
Liu, Weijun
Doihara, Hiroyoshi
Date, Hiroshi
Wan, Yong
[J]. CLINICAL CANCER RESEARCH, 2008, 14 (07) : 1966 - 1975

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