• 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

利用物理化学的片段构建方法破坏 CK2β 的组成性同二聚体蛋白-蛋白界面。

Disrupting the Constitutive, Homodimeric Protein-Protein Interface in CK2β Using a Biophysical Fragment-Based Approach.

机构信息

Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge, CB2 1EW, United Kingdom.

出版信息

J Am Chem Soc. 2016 Nov 2;138(43):14303-14311. doi: 10.1021/jacs.6b07440. Epub 2016 Oct 20.

DOI:10.1021/jacs.6b07440
PMID:27726344
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5257173/
Abstract

Identifying small molecules that induce the disruption of constitutive protein-protein interfaces is a challenging objective. Here, a targeted biophysical screening cascade was employed to specifically identify small molecules that could disrupt the constitutive, homodimeric protein-protein interface within CK2β. This approach could potentially be applied to achieve subunit disassembly of other homo-oligomeric proteins as a means of modulating protein function.

摘要

鉴定能够诱导组成型蛋白质-蛋白质界面破坏的小分子是一个具有挑战性的目标。在这里，采用了靶向生物物理筛选级联方法，专门鉴定能够破坏 CK2β 内组成型同源二聚体蛋白质-蛋白质界面的小分子。这种方法可能被应用于实现其他同源寡聚体蛋白质的亚基解体，作为调节蛋白质功能的一种手段。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/5257173/acb2df7aaf37/ja-2016-074403_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/5257173/521dbf534419/ja-2016-074403_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/5257173/a26ba133bc7e/ja-2016-074403_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/5257173/f4b132986155/ja-2016-074403_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/5257173/acb2df7aaf37/ja-2016-074403_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/5257173/521dbf534419/ja-2016-074403_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/5257173/a26ba133bc7e/ja-2016-074403_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/5257173/f4b132986155/ja-2016-074403_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/5257173/acb2df7aaf37/ja-2016-074403_0004.jpg

相似文献

1
Disrupting the Constitutive, Homodimeric Protein-Protein Interface in CK2β Using a Biophysical Fragment-Based Approach.利用物理化学的片段构建方法破坏 CK2β 的组成性同二聚体蛋白-蛋白界面。
J Am Chem Soc. 2016 Nov 2;138(43):14303-14311. doi: 10.1021/jacs.6b07440. Epub 2016 Oct 20.
2
Interaction between CK2α and CK2β, the subunits of protein kinase CK2: thermodynamic contributions of key residues on the CK2α surface.蛋白激酶 CK2 的亚基 CK2α 和 CK2β 之间的相互作用：CK2α 表面关键残基的热力学贡献。
Biochemistry. 2011 Feb 1;50(4):512-22. doi: 10.1021/bi1013563. Epub 2010 Dec 31.
3
Structure of the human protein kinase CK2 catalytic subunit CK2α' and interaction thermodynamics with the regulatory subunit CK2β.人蛋白激酶 CK2 催化亚基 CK2α'的结构及其与调节亚基 CK2β的相互作用热力学。
J Mol Biol. 2011 Mar 18;407(1):1-12. doi: 10.1016/j.jmb.2011.01.020. Epub 2011 Jan 15.
4
Structure-based design of small peptide inhibitors of protein kinase CK2 subunit interaction.基于结构的蛋白激酶CK2亚基相互作用小肽抑制剂的设计
Biochem J. 2007 Dec 15;408(3):363-73. doi: 10.1042/BJ20070825.
5
The interaction of CK2alpha and CK2beta, the subunits of protein kinase CK2, requires CK2beta in a preformed conformation and is enthalpically driven.蛋白激酶CK2的亚基CK2α和CK2β之间的相互作用需要处于预先形成构象的CK2β，并且是由焓驱动的。
Protein Sci. 2008 Dec;17(12):2180-6. doi: 10.1110/ps.037770.108. Epub 2008 Sep 29.
6
First inactive conformation of CK2 alpha, the catalytic subunit of protein kinase CK2.蛋白激酶CK2的催化亚基CK2α的首个无活性构象。
J Mol Biol. 2009 Mar 13;386(5):1212-21. doi: 10.1016/j.jmb.2009.01.033. Epub 2009 Jan 24.
7
Structural basis of the constitutive activity of protein kinase CK2.蛋白激酶CK2组成型活性的结构基础
Methods Enzymol. 2010;484:515-29. doi: 10.1016/B978-0-12-381298-8.00025-3.
8
Enriching screening libraries with bioactive fragment space.用生物活性片段空间丰富筛选文库。
Bioorg Med Chem Lett. 2016 Aug 1;26(15):3594-7. doi: 10.1016/j.bmcl.2016.06.013. Epub 2016 Jun 7.
9
Screening of fibrillogenesis inhibitors of β2-microglobulin: integrated strategies by mass spectrometry capillary electrophoresis and in silico simulations.β2-微球蛋白纤维形成抑制剂的筛选：质谱毛细管电泳和计算机模拟的综合策略。
Anal Chim Acta. 2011 Jan 31;685(2):153-61. doi: 10.1016/j.aca.2010.11.025. Epub 2010 Nov 19.
10
From determinants of RUNX1/ETO tetramerization to small-molecule protein-protein interaction inhibitors targeting acute myeloid leukemia.从 RUNX1/ETO 四聚体形成的决定因素到针对急性髓系白血病的小分子蛋白-蛋白相互作用抑制剂。
J Chem Inf Model. 2013 Sep 23;53(9):2197-202. doi: 10.1021/ci400332e. Epub 2013 Sep 12.

引用本文的文献

1
Fragment-based drug discovery campaigns guided by native mass spectrometry.基于天然质谱的片段药物发现研究
RSC Med Chem. 2024 May 22;15(7):2270-2285. doi: 10.1039/d4md00273c. eCollection 2024 Jul 17.
2
Target-based drug discovery: Applications of fluorescence techniques in high throughput and fragment-based screening.基于靶点的药物发现：荧光技术在高通量筛选和基于片段的筛选中的应用。
Heliyon. 2023 Dec 19;10(1):e23864. doi: 10.1016/j.heliyon.2023.e23864. eCollection 2024 Jan 15.
3
MEP pathway products allosterically promote monomerization of deoxy-D-xylulose-5-phosphate synthase to feedback-regulate their supply.

本文引用的文献

1
Characterization of Ligand Binding by Saturation Transfer Difference NMR Spectroscopy.通过饱和转移差核磁共振波谱法对配体结合进行表征
Angew Chem Int Ed Engl. 1999 Jun 14;38(12):1784-1788. doi: 10.1002/(SICI)1521-3773(19990614)38:12<1784::AID-ANIE1784>3.0.CO;2-Q.
2
Fragment-Based Protein-Protein Interaction Antagonists of a Viral Dimeric Protease.病毒二聚体蛋白酶的基于片段的蛋白质-蛋白质相互作用拮抗剂
ChemMedChem. 2016 Apr 19;11(8):862-9. doi: 10.1002/cmdc.201500526. Epub 2016 Jan 28.
3
Small-Molecule Disruption of RAD52 Rings as a Mechanism for Precision Medicine in BRCA-Deficient Cancers.
MEP 途径产物别构促进脱氧-D-木酮糖-5-磷酸合酶单体化，以反馈调节其供应。
Plant Commun. 2023 May 8;4(3):100512. doi: 10.1016/j.xplc.2022.100512. Epub 2022 Dec 26.
4
: An Screening Targeting HCMV ppUL44 Processivity Factor Homodimerization Identifies Small Molecules Inhibiting Viral Replication.: 一种针对 HCMV ppUL44 连续性因子同源二聚体的筛选靶标，可识别抑制病毒复制的小分子。
Viruses. 2021 May 20;13(5):941. doi: 10.3390/v13050941.
5
Development of a Robust High-Throughput Screening Platform for Inhibitors of the Striatal-Enriched Tyrosine Phosphatase (STEP).开发一种用于抑制纹状体丰富的酪氨酸磷酸酶（STEP）的稳健高通量筛选平台。
Int J Mol Sci. 2021 Apr 23;22(9):4417. doi: 10.3390/ijms22094417.
6
Downfalls of Chemical Probes Acting at the Kinase ATP-Site: CK2 as a Case Study.作用于激酶 ATP 结合位点的化学探针的局限性：以 CK2 为例。
Molecules. 2021 Mar 31;26(7):1977. doi: 10.3390/molecules26071977.
7
Discovery of a novel lactate dehydrogenase tetramerization domain using epitope mapping and peptides.利用表位作图和肽段发现新型乳酸脱氢酶四聚化结构域。
J Biol Chem. 2021 Jan-Jun;296:100422. doi: 10.1016/j.jbc.2021.100422. Epub 2021 Feb 17.
8
Small molecule-based targeting of TTD-A dimerization to control TFIIH transcriptional activity represents a potential strategy for anticancer therapy.基于小分子的 TTD-A 二聚化靶向以控制 TFIIH 转录活性代表了一种潜在的抗癌治疗策略。
J Biol Chem. 2018 Sep 28;293(39):14974-14988. doi: 10.1074/jbc.RA118.003444. Epub 2018 Aug 1.
小分子破坏RAD52环作为BRCA缺陷型癌症精准医学的一种机制
Chem Biol. 2015 Nov 19;22(11):1491-1504. doi: 10.1016/j.chembiol.2015.10.003. Epub 2015 Nov 5.
4
Fragment-based exploration of binding site flexibility in Mycobacterium tuberculosis BioA.基于片段的结核分枝杆菌BioA中结合位点灵活性探索
J Med Chem. 2015 Jul 9;58(13):5208-17. doi: 10.1021/acs.jmedchem.5b00092. Epub 2015 Jun 24.
5
What Glues a Homodimer Together: Systematic Analysis of the Stabilizing Effect of an Aromatic Hot Spot in the Protein-Protein Interface of the tRNA-Modifying Enzyme Tgt.是什么将同二聚体结合在一起：对tRNA修饰酶Tgt蛋白质-蛋白质界面中一个芳香族热点稳定作用的系统分析。
ACS Chem Biol. 2015 Aug 21;10(8):1897-907. doi: 10.1021/acschembio.5b00028. Epub 2015 May 26.
6
Small-molecule inhibitors of protein-protein interactions: progressing toward the reality.蛋白质-蛋白质相互作用的小分子抑制剂：迈向现实
Chem Biol. 2014 Sep 18;21(9):1102-14. doi: 10.1016/j.chembiol.2014.09.001.
7
Development of a high-throughput screening-compatible assay to identify inhibitors of the CK2α/CK2β interaction.开发一种与高通量筛选兼容的检测方法，以鉴定CK2α/CK2β相互作用的抑制剂。
Anal Biochem. 2015 Jan 1;468:4-14. doi: 10.1016/j.ab.2014.09.003. Epub 2014 Sep 16.
8
Inhibition of Mycobacterium tuberculosis transaminase BioA by aryl hydrazines and hydrazides.芳基肼和酰肼对结核分枝杆菌转氨酶BioA的抑制作用。
Chembiochem. 2014 Mar 3;15(4):575-86. doi: 10.1002/cbic.201300748. Epub 2014 Jan 31.
9
Screening protein-small molecule interactions by NMR.通过核磁共振筛选蛋白质-小分子相互作用
Methods Mol Biol. 2013;1008:389-413. doi: 10.1007/978-1-62703-398-5_14.
10
Fragment-based approaches in drug discovery and chemical biology.基于片段的药物发现和化学生物学方法。
Biochemistry. 2012 Jun 26;51(25):4990-5003. doi: 10.1021/bi3005126. Epub 2012 Jun 14.