中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Structural Mass Spectrometry Probes the Inhibitor-Induced Allosteric Activation of CDK12/CDK13-Cyclin K Dissociation

文献类型：期刊论文

作者Bai, Yu2,3,4; Liu, Zheyi3,5; Li, Yuanqing1,5,6; Zhao, Heng3,4; Lai, Can3,4,5; Zhao, Shan3,4; Chen, Kaixian1,5,6; Luo, Cheng5,6; Yang, Xueming4; Wang, Fangjun3,4,5
刊名JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
出版日期2023-05-19
卷号145期号:21页码:11477-11481
ISSN号0002-7863
DOI10.1021/jacs.3c01697
通讯作者Luo, Cheng(cluo@simm.ac.cn) ; Wang, Fangjun(wangfj@dicp.ac.cn)
英文摘要The rational design and developmentof effective inhibitorsforcyclin-dependent kinases 12 and 13 (CDK12 and CDK13) are largely dependenton the understanding of the dynamic inhibition conformations but aredifficult to be achieved by conventional characterization tools. Herein,we integrate the structural mass spectrometry (MS) methods of lysinereactivity profiling (LRP) and native MS (nMS) to systematically interrogateboth the dynamic molecular interactions and overall protein assemblyof CDK12/CDK13-cyclin K (CycK) complexes under the modulation of smallmolecule inhibitors. The essential structure insights, including inhibitorbinding pocket, binding strength, interfacial molecular details, anddynamic conformation changes, can be derived from the complementaryresults of LRP and nMS. We find the inhibitor SR-4835 binding cangreatly destabilize the CDK12/CDK13-CycK interactions in an unusualallosteric activation way, thereby providing a novel alternative forthe kinase activity inhibition. Our results underscore the great potentialof LRP combination with nMS for the evaluation and rational designof effective kinase inhibitors at the molecular level.
WOS关键词CDK12 ; CYCLIN
资助项目National Key R&D Program of China[2022YFC3400502] ; National Natural Science Foundation of China[32088101] ; National Natural Science Foundation of China[92253304] ; National Natural Science Foundation of China[22288201] ; Scientific Instrument Developing Project of the Chinese Academy of Sciences[GJJSTD20220001] ; Scientific Instrument Developing Project of the Chinese Academy of Sciences[LG-QS-202206-07] ; DICP[DICP I202242]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001011049000001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/306230]  
专题新药研究国家重点实验室
通讯作者Luo, Cheng; Wang, Fangjun
作者单位1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
2.China Med Univ, Sch Pharm, Shenyang 110122, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China
4.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Dalian 116023, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Ctr Chem Biol,State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Bai, Yu,Liu, Zheyi,Li, Yuanqing,et al. Structural Mass Spectrometry Probes the Inhibitor-Induced Allosteric Activation of CDK12/CDK13-Cyclin K Dissociation[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2023,145(21):11477-11481.
APA Bai, Yu.,Liu, Zheyi.,Li, Yuanqing.,Zhao, Heng.,Lai, Can.,...&Wang, Fangjun.(2023).Structural Mass Spectrometry Probes the Inhibitor-Induced Allosteric Activation of CDK12/CDK13-Cyclin K Dissociation.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,145(21),11477-11481.
MLA Bai, Yu,et al."Structural Mass Spectrometry Probes the Inhibitor-Induced Allosteric Activation of CDK12/CDK13-Cyclin K Dissociation".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 145.21(2023):11477-11481.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。