• 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

通过分子动力学模拟探索不同 CagA 癌蛋白和 SHP2 的独特结合和激活机制。

Exploring the Distinct Binding and Activation Mechanisms for Different CagA Oncoproteins and SHP2 by Molecular Dynamics Simulations.

机构信息

Edmond H. Fischer Signal Transduction Laboratory, College of Life Sciences, Jilin University, Changchun 130023, China.

Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry, Jilin University, Changchun 130023, China.

出版信息

Molecules. 2021 Feb 5;26(4):837. doi: 10.3390/molecules26040837.

DOI:10.3390/molecules26040837
PMID:33562680
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7916045/
Abstract

CagA is a major virulence factor of . CagA is geographically subclassified into East Asian CagA and Western CagA, which are characterized by the presence of a EPIYA-D or EPIYA-C segment. The East Asian CagA is more closely associated with gastric cancer than the Western CagA. In this study, molecular dynamic (MD) simulations were performed to investigate the binding details of SHP2 and EPIYA segments, and to explore the allosteric regulation mechanism of SHP2. Our results show that the EPIYA-D has a stronger binding affinity to the N-SH2 domain of SHP2 than EPIYA-C. In addition, a single EPIYA-D binding to N-SH2 domain of SHP2 can cause a deflection of the key helix B, and the deflected helix B could squeeze the N-SH2 and PTP domains to break the autoinhibition pocket of SHP2. However, a single EPIYA-C binding to the N-SH2 domain of SHP2 cannot break the autoinhibition of SHP2 because the secondary structure of the key helix B is destroyed. However, the tandem EPIYA-C not only increases its binding affinity to SHP2, but also does not significantly break the secondary structure of the key helix B. Our study can help us better understand the mechanism of gastric cancer caused by infection.

摘要

CagA 是 的主要毒力因子。CagA 按地域分为东亚 CagA 和西方 CagA，其特征是存在 EPIYA-D 或 EPIYA-C 片段。东亚 CagA 与胃癌的相关性比西方 CagA 更强。在这项研究中，进行了分子动力学（MD）模拟，以研究 SHP2 和 EPIYA 片段的结合细节，并探索 SHP2 的变构调节机制。我们的结果表明，EPIYA-D 与 SHP2 的 N-SH2 结构域的结合亲和力强于 EPIYA-C。此外，单个 EPIYA-D 结合到 SHP2 的 N-SH2 结构域可以导致关键螺旋 B 的偏斜，并且偏斜的螺旋 B 可以挤压 N-SH2 和 PTP 结构域以破坏 SHP2 的自动抑制口袋。然而，单个 EPIYA-C 结合到 SHP2 的 N-SH2 结构域不能破坏 SHP2 的自动抑制，因为关键螺旋 B 的二级结构被破坏。然而，串联的 EPIYA-C 不仅增加了与 SHP2 的结合亲和力，而且对关键螺旋 B 的二级结构没有明显的破坏。我们的研究可以帮助我们更好地了解 感染引起胃癌的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/6fe1ac5d7fc5/molecules-26-00837-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/1909c5187d11/molecules-26-00837-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/bb89cb72c034/molecules-26-00837-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/cde88b7928b8/molecules-26-00837-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/b6b24318204f/molecules-26-00837-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/3684e7a1b802/molecules-26-00837-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/0e605d292cec/molecules-26-00837-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/e5af9cf9bbee/molecules-26-00837-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/0a8e41a1c37e/molecules-26-00837-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/6fe1ac5d7fc5/molecules-26-00837-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/1909c5187d11/molecules-26-00837-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/bb89cb72c034/molecules-26-00837-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/cde88b7928b8/molecules-26-00837-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/b6b24318204f/molecules-26-00837-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/3684e7a1b802/molecules-26-00837-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/0e605d292cec/molecules-26-00837-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/e5af9cf9bbee/molecules-26-00837-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/0a8e41a1c37e/molecules-26-00837-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e95/7916045/6fe1ac5d7fc5/molecules-26-00837-g009.jpg

相似文献

1
Exploring the Distinct Binding and Activation Mechanisms for Different CagA Oncoproteins and SHP2 by Molecular Dynamics Simulations.通过分子动力学模拟探索不同 CagA 癌蛋白和 SHP2 的独特结合和激活机制。
Molecules. 2021 Feb 5;26(4):837. doi: 10.3390/molecules26040837.
2
Differential Mechanisms for SHP2 Binding and Activation Are Exploited by Geographically Distinct Helicobacter pylori CagA Oncoproteins.不同地理来源的幽门螺杆菌 CagA 癌蛋白通过不同的机制与 SHP2 结合并激活其活性。
Cell Rep. 2017 Sep 19;20(12):2876-2890. doi: 10.1016/j.celrep.2017.08.080.
3
Helicobacter pylori CagA oncoprotein interacts with SHIP2 to increase its delivery into gastric epithelial cells.幽门螺杆菌 CagA 癌蛋白与 SHIP2 相互作用，增加其进入胃上皮细胞的传递。
Cancer Sci. 2020 May;111(5):1596-1606. doi: 10.1111/cas.14391. Epub 2020 Apr 13.
4
Dramatic increase in SHP2 binding activity of Helicobacter pylori Western CagA by EPIYA-C duplication: its implications in gastric carcinogenesis.幽门螺杆菌 Western CagA 的 SHP2 结合活性因 EPIYA-C 重复而显著增加：其在胃癌发生中的意义。
Sci Rep. 2015 Oct 28;5:15749. doi: 10.1038/srep15749.
5
Malignant Helicobacter pylori-Associated Diseases: Gastric Cancer and MALT Lymphoma.恶性幽门螺杆菌相关疾病：胃癌和 MALT 淋巴瘤。
Adv Exp Med Biol. 2019;1149:135-149. doi: 10.1007/5584_2019_363.
6
Intramolecular energies of the cytotoxic protein CagA of Helicobacter pylori as a possible descriptor of strains' pathogenicity level.幽门螺杆菌细胞毒性蛋白 CagA 的分子内能量可作为菌株致病性水平的一个可能描述符。
Comput Biol Chem. 2018 Oct;76:17-22. doi: 10.1016/j.compbiolchem.2018.05.016. Epub 2018 May 25.
7
Evaluating the origin and virulence of a Helicobacter pylori cagA-positive strain isolated from a non-human primate.评估一株来源于非人灵长类动物的 cagA 阳性幽门螺杆菌的起源和毒力。
Sci Rep. 2018 Oct 29;8(1):15981. doi: 10.1038/s41598-018-34425-4.
8
Systematic analysis of phosphotyrosine antibodies recognizing single phosphorylated EPIYA-motifs in CagA of East Asian-type Helicobacter pylori strains.对识别东亚型幽门螺杆菌菌株CagA中单个磷酸化EPIYA基序的磷酸酪氨酸抗体的系统分析。
BMC Microbiol. 2016 Sep 2;16(1):201. doi: 10.1186/s12866-016-0820-6.
9
Natural variant of the Helicobacter pylori CagA oncoprotein that lost the ability to interact with PAR1.失去与 PAR1 相互作用能力的幽门螺杆菌 CagA 癌蛋白的天然变异体。
Cancer Sci. 2014 Mar;105(3):245-51. doi: 10.1111/cas.12342. Epub 2014 Feb 12.
10
East Asian type CagA hijacks more SHIP2 by its EPIYA-D motif to potentiate the oncogenicity.东亚型 CagA 通过其 EPIYA-D 基序劫持更多的 SHIP2，从而增强致癌性。
Virulence. 2024 Dec;15(1):2375549. doi: 10.1080/21505594.2024.2375549. Epub 2024 Jul 9.

引用本文的文献

1
A review of signal pathway induced by virulent protein CagA of .一种毒力蛋白 CagA 诱导的信号通路综述
Front Cell Infect Microbiol. 2023 Apr 14;13:1062803. doi: 10.3389/fcimb.2023.1062803. eCollection 2023.
2
Role of SHP2/PTPN11 in the occurrence and prognosis of cancer: A systematic review and meta-analysis.SHP2/PTPN11在癌症发生及预后中的作用：一项系统评价与Meta分析
Oncol Lett. 2022 Nov 22;25(1):19. doi: 10.3892/ol.2022.13605. eCollection 2023 Jan.
3
Discriminating between competing models for the allosteric regulation of oncogenic phosphatase SHP2 by characterizing its active state.

本文引用的文献

1
Exploring the Allosteric Mechanism of Src Homology-2 Domain-Containing Protein Tyrosine Phosphatase 2 (SHP2) by Molecular Dynamics Simulations.通过分子动力学模拟探索含Src同源2结构域蛋白酪氨酸磷酸酶2（SHP2）的变构机制
Front Chem. 2020 Nov 23;8:597495. doi: 10.3389/fchem.2020.597495. eCollection 2020.
2
SHP2 promotes proliferation of breast cancer cells through regulating Cyclin D1 stability the PI3K/AKT/GSK3β signaling pathway.SHP2 通过调节细胞周期蛋白 D1 的稳定性来促进乳腺癌细胞的增殖，该过程涉及到 PI3K/AKT/GSK3β 信号通路。
Cancer Biol Med. 2020 Aug 15;17(3):707-725. doi: 10.20892/j.issn.2095-3941.2020.0056.
3
通过表征致癌磷酸酶SHP2的活性状态来区分其变构调节的竞争模型。
Comput Struct Biotechnol J. 2021 Nov 3;19:6125-6139. doi: 10.1016/j.csbj.2021.10.041. eCollection 2021.
MolAICal: a soft tool for 3D drug design of protein targets by artificial intelligence and classical algorithm.
MolAICal：一款基于人工智能和经典算法的蛋白质靶标三维药物设计的软工具。
Brief Bioinform. 2021 May 20;22(3). doi: 10.1093/bib/bbaa161.
4
Therapeutic potential of targeting SHP2 in human developmental disorders and cancers.靶向 SHP2 在人类发育障碍和癌症中的治疗潜力。
Eur J Med Chem. 2020 Mar 15;190:112117. doi: 10.1016/j.ejmech.2020.112117. Epub 2020 Feb 6.
5
Epidemiology of gastric cancer: global trends, risk factors and prevention.胃癌流行病学：全球趋势、风险因素与预防
Prz Gastroenterol. 2019;14(1):26-38. doi: 10.5114/pg.2018.80001. Epub 2018 Nov 28.
6
Allostery in Its Many Disguises: From Theory to Applications.变构作用的多种伪装：从理论到应用。
Structure. 2019 Apr 2;27(4):566-578. doi: 10.1016/j.str.2019.01.003. Epub 2019 Feb 7.
7
Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2.磷酸酶 SHP2 激活突变和别构药物抑制的作用机制。
Nat Commun. 2018 Oct 30;9(1):4507. doi: 10.1038/s41467-018-06814-w.
8
Dual Allosteric Inhibition of SHP2 Phosphatase.双重变构抑制 SHP2 磷酸酶。
ACS Chem Biol. 2018 Mar 16;13(3):647-656. doi: 10.1021/acschembio.7b00980. Epub 2018 Jan 18.
9
Differential Mechanisms for SHP2 Binding and Activation Are Exploited by Geographically Distinct Helicobacter pylori CagA Oncoproteins.不同地理来源的幽门螺杆菌 CagA 癌蛋白通过不同的机制与 SHP2 结合并激活其活性。
Cell Rep. 2017 Sep 19;20(12):2876-2890. doi: 10.1016/j.celrep.2017.08.080.
10
Structure and function of Helicobacter pylori CagA, the first-identified bacterial protein involved in human cancer.幽门螺杆菌CagA的结构与功能，CagA是首个被鉴定出的与人类癌症相关的细菌蛋白。
Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(4):196-219. doi: 10.2183/pjab.93.013.