《WD40重複蛋白家族的結構與熱點胺基酸預測與藥物設計》是吳雲東為項目負責人，北京大學為依託單位的重點項目。
基本介紹
- 中文名：WD40重複蛋白家族的結構與熱點胺基酸預測與藥物設計
- 項目類別 ：重點項目
- 項目負責人：吳雲東
- 依託單位 ：北京大學
科研成果,項目摘要,
科研成果
序號 | 標題 | 類型 | 作者 |
|---|---|---|---|
1 | 中國化學會-物理有機化學成就獎 | 科研獎勵 | 吳雲東| |
2 | 洪堡獎 | 科研獎勵 | 吳雲東| |
3 | Robert S. Mulliken Lecture獎 | 科研獎勵 | 吳雲東| |
4 | 2014FuKui獎 | 科研獎勵 | 吳雲東| |
5 | 安徽省科學技術獎 | 科研獎勵 | 北京大學| |
6 | 國家自然科學獎 | 科研獎勵 | 吳雲東| |
7 | Total Synthesis and Stereochemical Assignment of Callyspongiolide | 期刊論文 | J. J. Zhou|B. W. Gao|Z. S. Xu|T. Ye| |
8 | New Mechanistic Insights on the Selectivity of Transition-Metal-Catalyzed Organic Reactions: The Role of Computational Chemistry | 期刊論文 | X. H. Zhang|L. W. Chung|Y. D. Wu| |
9 | Total synthesis of padanamides A and B | 期刊論文 | Liu, Yuqing|Zhang, Hui|Xu, Zhengshuang|Ye, Tao| |
10 | Mechanistic Study on Pd/Mono-N-protected Amino Acid Catalyzed Vinyl-Vinyl Coupling Reactions: Reactivity and E/Z Selectivity | 期刊論文 | G. J. Cheng|P. Chen|X. H. Zhang|Y. D. Wu| |
11 | Inhibition and Mechanism of HDAC8 Revisited.？ | 期刊論文 | Chen K|Zhang XX|Wu YD|Wiest O| |
12 | Mechanism of Ni-NHC Catalyzed Hydrogenolysis of Aryl Ethers: Roles of the Excess Base | 期刊論文 | Xu, Liping|Chung, Lung Wa|Wu, Yun-Dong| |
13 | Mechanism and Selectivity in the Pd-Catalyzed Difunctionalization of Isoprene | 期刊論文 | M. S. McCammant|M. S. Sigman|Y. D. Wu|O. Wiest| |
14 | Total synthesis of largamide B | 期刊論文 | Wang, Xiaoji|Chen, Shipeng|Xu, Zhengshuang|Ye, Tao| |
15 | Palladium-catalyzed benzo[d]isoxazole synthesis by C-H activation/[4+1] annulation | 期刊論文 | Wu, Yun-Dong|Wang, Dongqi|Zhang, Xinhao|Zhao, Jing| |
16 | Mechanism, Reactivity, and Selectivity in Palladium-Catalyzed Redox-Relay Heck Arylations of Alkenyl Alcohols | 期刊論文 | Norrby, Per-Ola|Wu, Yun-Dong|Sigman, Matthew S.|Wiest, Olaf| |
17 | Investigating the Nature of Palladium Chain-Walking in the Enantioselective Redox-Relay Heck Reaction of Alkenyl Alcohols | 期刊論文 | P. O. Norrby|Y. D. Wu|O. Wiest|M. S. Sigman| |
18 | Total Synthesis of Incarvilleatone and Incarviditone: Insight into Their Biosynthetic Pathways and Structure Determination | 期刊論文 | Hai Shang|Xinhao zhang|Yun-Dong Wu|Yefeng Tang| |
19 | Accurate Structure Prediction and Conformational Analysis of Cyclic Peptides with Residue-Specific Force Fields | 期刊論文 | H. Geng|F. Jiang|Y. D. Wu| |
20 | Folding of Fourteen Small Proteins with a Residue-Specific Force Field and Replica-Exchange Molecular Dynamics | 期刊論文 | Jiang, Fan|Wu, Yun-Dong| |
21 | Silicon-Containing Formal 4 pi-Electron Four-Membered Ring Systems: Antiaromatic, Aromatic, or Nonaromatic? | 期刊論文 | Jun Zhu|Xinhao Zhang|Shigeyoshi Inoue|Yun-Dong Wu| |
22 | Regulation of DNA replication and chromosomal polyploidy by the MLL-WDR5-RBBP5 methyltransferases | 期刊論文 | I. S. Mihaylov|J. Yu|H. Sun|H. Zhang| |
23 | Non-manifesting AHI1 truncations indicate localized loss-of-function tolerance in a severe Mendelian disease gene | 期刊論文 | Gleeson, Joseph|Boltshauser, Eugen|Westerfield, Monte|Bolz, Hanno J.| |
24 | Fenofibrate increases heme oxygenase 1 expression and astrocyte proliferation while limits neuronal injury during intracerebral hemorrhage | 期刊論文 | A. L. Guan|C. H. Xing|F. Lu|X. P. Ji| |
25 | Pluripotent Stem Cell Protein Sox2 Confers Sensitivity to LSD1 Inhibition in Cancer Cells | 期刊論文 | Y. Liu|H. Sun|T. Ye|H. Zhang| |
26 | Ir-Catalyzed Regio- and Stereoselective Hydrosilylation of Internal Thioalkynes: A Combined Experimental and Computational Study | 期刊論文 | Y. Wang|X. H. Zhang|Y. D. Wu|J. W. Sun| |
27 | Reactions of a tungsten alkylidyne complex with mono-dentate phosphines: Thermodynamic and theoretical studies | 期刊論文 | Dougan, Brenda A.|Zhang, Xinhao|Wu, Yun-Dong|Xue, Zi-Ling| |
28 | Total Synthesis and Biological Evaluation of Grassypeptolide A | 期刊論文 | Luesch, Hendrik|Zhang, Hui|Xu, Zhengshuang|Ye, Tao| |
29 | The intrinsic conformational features of amino acids from a protein coil library and their applications in force field development | 期刊論文 | Jiang, Fan|Han, Wei|Wu, Yun-Dong| |
30 | A Method for WD40 Repeat Detection and Secondary Structure Prediction | 期刊論文 | Jiang, Fan|Zhuo, Zhu|Wu, Xian-Hui|Wu, Yun-Dong| |
31 | WDSPdb: a database for WD40-repeat proteins | 期刊論文 | Zou, Xu-Dong|Wu, Xian-Hui|Ye, Zhi-Qiang|Wu, Yun-Dong| |
32 | A novel CyclinE/CyclinA-CDK Inhibitor targets p27(Kip1) degradation, cell cycle progression and cell survival: Implications in cancer therapy | 期刊論文 | Maguire, Anita R.|Quan, Junmin|Zhang, Hui|Ye, Tao| |
33 | Computational Exploration of Zinc Binding Groups for HDAC Inhibition | 期刊論文 | Chen, Kai|Xu, Liping|Wiest, Olaf| |
34 | Concise Total Synthesis of Nannocystin A | 期刊論文 | L. P. Liao|J. J. Zhou|Z. S. Xu|T. Ye| |
35 | Palladium-Catalyzed Meta-Selective C-H Bond Activation with a Nitrile-Containing Template: Computational Study on Mechanism and Origins of Selectivity | 期刊論文 | Zhang, Xinhao|Yu, Jin-Quan|Wu, Yun-Dong|Houk, K. N.| |
36 | Ligand-Controlled Reactivity, Selectivity, and Mechanism of Cationic Ruthenium-Catalyzed Hydrosilylations of Alkynes, Ketones, and Nitriles: A Theoretical Study | 期刊論文 | Chung, Lung Wa|Zhang, Xinhao|Houk, K. N.|Wu, Yun-Dong| |
37 | Role of N-Acyl Amino Acid Ligands in Pd(II)-Catalyzed Remote C-H Activation of Tethered Arenes | 期刊論文 | Zhang, Xinhao|Houk, K. N.|Yu, Jin-Quan|Wu, Yun-Dong| |
38 | Identifying the Hotspots on the Top Faces of WD40-Repeat Proteins from Their Primary Sequences by beta-Bulges and DHSW Tetrads | 期刊論文 | Yang Wang|Zhu Zhuo|Fan Jiang|Yun-Dong Wu| |
39 | Mitotic phosphorylation of SOX2 mediated by Aurora kinase A is critical for the stem-cell like cell maintenance in PA-1 cells | 期刊論文 | M. Yu|R. F. Lan|S. M. Li|F. Lu| |
40 | Genome-wide Analysis of WD40 Protein Family in Human. | 期刊論文 | Ma, Jing|Li, Tuan|Ye, Zhi-Qiang|Wu, Yun-Dong| |
41 | Mutation of POC1B in a severe syndromic retinal ciliopathy. | 期刊論文 | Fry, Andrew M|Westerfield, Monte|Wolfrum, Uwe|Bolz, Hanno J| |
42 | LSD1 Regulates Pluripotency of Embryonic Stem/Carcinoma Cells through Histone Deacetylase 1-Mediated Deacetylation of Histone H4 at Lysine 16 | 期刊論文 | Ye, Tao|Sun, Hong|Lu, Fei|Zhang, Hui| |
43 | Conjugate Addition vs Heck Reaction: A Theoretical Study on Competitive Coupling Catalyzed by Isoelectronic Metal (Pd(II) and Rh(I)) | 期刊論文 | Qian Peng|Hong Yan|Xinhao Zhang|Yun-Dong Wu| |
44 | Computational Exploration of Rh-III/Rh-V and Rh-III/Rh-I Catalysis in Rhodium(III)-Catalyzed C-H Activation Reactions of N-Phenoxyacetamides with Alkynes | 期刊論文 | Y. F. Yang|K. N. Houk|Y. D. Wu| |
45 | Enantioselective Formation of Cyano-Bearing All-Carbon Quaternary Stereocenters: Desymmetrization by Copper-Catalyzed N-Arylation | 期刊論文 | Zhang, Shasha|Wu, Yun-Dong|Zhang, Xinhao|Cai, Qian| |
46 | Residue-Specific Force Field Based on Protein Coil Library. RSFF2: Modification of AMBER ff99SB | 期刊論文 | Zhou, Chen-Yang|Jiang, Fan|Wu, Yun-Dong| |
47 | Highly Regio- and Stereoselective Hydrosilylation of Internal Thioalkynes under Mild Conditions | 期刊論文 | Zhang, Xinhao|Chung, Lung Wa|Wu, Yun-Dong|Sun, Jianwei| |
48 | Why does Togni's reagent I exist in the high-energy hypervalent iodine form? Re-evaluation of benziodoxole based hypervalent iodine reagents | 期刊論文 | Xie, Yaoming|Wu, Yun-Dong|Zhang, Xinhao|Schaefer, Henry F., III| |
49 | Folding Thermodynamics and Mechanism of Five Trp-Cage Variants from Replica-Exchange MD Simulations with RSFF2 Force Field | 期刊論文 | Zhou, Chen-Yang|Jiang, Fan|Wu, Yun-Dong| |
50 | Ligand-Controlled Remarkable Regio- and Stereodivergence in Intermolecular Hydrosilylation of Internal Alkynes: Experimental and Theoretical Studies | 期刊論文 | Chung, Lung Wa|Zhang, Xinhao|Sun, Jianwei|Wu, Yun-Dong| |
51 | Acid sphingomyelinase is required for cell surface presentation of Met receptor tyrosine kinase in cancer cells | 期刊論文 | N. Okada|F. Lu|H. Zhang|H. Sun| |
52 | Computational Studies on the Mechanism of the Copper-Catalyzed sp(3)-C-H Cross-Dehydrogenative Coupling Reaction | 期刊論文 | Yang, Yun-Fang|Zhang, Xinhao|Wiest, Olaf|Wu, Yun-Dong| |
53 | Ligand-Assisted Palladium(II)/(IV) Oxidation for sp(3) CH Fluorination | 期刊論文 | P. Chen|Y. D. Wu|X. H. Zhang|Y. Huang| |
54 | Folding Simulations of an alpha-Helical Hairpin Motif alpha t alpha with Residue-Specific Force Fields | 期刊論文 | Zeng, Juan|Jiang, Fan|Wu, Yun-Dong| |
55 | Nudibaccatumone, a Trimer Comprising a Phenylpropanoid and Two Sesquiterpene Moieties from Piper nudibaccatum | 期刊論文 | Yang, Fu-Mei|Hu, Guang-Wan|Wang, Yue-Hu|Long, Chun-Lin| |
56 | SILAC-based quantitative proteomics identified lysosome as a fast response target to PDT agent Gd-N induced oxidative stress in human ovarian cancer IGROV1 cells | 期刊論文 | Wong, Wai-Kwok|Wong, Ka-Leung|Li, Shuiming|Lu, Fei| |
57 | Residue-Specific Force Field Based on the Protein Coil Library. RSFF1: Modification of OPLS-AA/L | 期刊論文 | Jiang, Fan|Zhou, Chen-Yang|Wu, Yun-Dong| |
58 | A diversity-oriented synthesis of bioactive benzanilides via a regioselective C(sp(2))-H hydroxylation strategy | 期刊論文 | Sun, Tian-Yu|Wu, Yun-Dong|Zhang, Xinhao|Rao, Yu| |
59 | The total synthesis and stereochemical assignment of scytonemin A | 期刊論文 | L. Wang|J. F. Zhang|Z. S. Xu|T. Ye| |
60 | Significant Refinement of Protein Structure Models Using a Residue-Specific Force Field | 期刊論文 | Xun, Sangni|Jiang, Fan|Wu, Yun-Dong| |
61 | Intrinsically disordered regions stabilize the helical form of the C-terminal domain of RfaH: A molecular dynamics study | 期刊論文 | S. N. Xun|F. Jiang|Y. D. Wu| |
62 | Dissecting the phenotypes of Plk1 inhibition in cancer cells using novel kinase inhibitory chemical CBB2001 | 期刊論文 | Ding, Yuan-Hua|Yang, Zhen|Lu, Fei|Zhang, Hui| |
63 | Total synthesis and stereochemical revision of lagunamide A | 期刊論文 | Wang, Zhuo|Liu, Yuqing|Xu, Zhengshuang|Ye, Tao| |
64 | Computational Organic Chemistry: Bridging Theory and Experiment in Establishing the Mechanisms of Chemical Reactions | 期刊論文 | Zhang, Xinhao|Chung, Lung Wa|Xu, Liping|Wu, Yun-Dong| |
項目摘要
WD40重複蛋白家族占真核生物總體蛋白種類的1%，是最大的蛋白質家族之一，其主要功能是通過蛋白質-蛋白質相互作用組裝各種不同的蛋白複合體，參與調控幾乎所有的生物學功能。WD40重複蛋白有關的異常調控與很多疾病有關係，是重要的潛在藥物靶點。本項目申請是基於我們已有的工作基礎，對已有35個WD40重複蛋白的晶體結構進行統計分析、結合結構生物學與分子生物學實驗，發展針對WD40重複蛋白家族的二級、三級結構以及熱點胺基酸的預測方法。利用該預測方法對WD40重複蛋白CDT2進行二級、三級結構以及熱點胺基酸預測，用於指導和幫助研究CDT2在PCNA的幫助下催化一系列調控DNA複製的底物蛋白的多泛素化、進一步闡明CDT2識別的底物蛋白的胺基酸序列以及結合模式，從而設計針對CDT2調控通道的小分子抑制劑。基於WDR5-H3K4/MLL晶體結構複合物，結合我們對於Hotspots的研究，設計環肽小分子抑制劑
