吴 更

姓名: 吴 更

职称: 研究员

E-Mail: Geng.wu@sjtu.edu.cn

个人主页:

联系电话:021-34205914

  • 个人简历:

    个人简介

    1997年在中国科学技术大学生物系获学士学位,2001年在普林斯顿大学化学系获博士学位。发表SCI论文44篇,被引用超过2200次。曾分别在NatureMolecular CellScience上发表第一作者论文,已分别被引用464次、281次和152次。所解析的Smac-XIAP蛋白质复合物的晶体结构被GenentechNovartis等制药公司作为研发抗癌药物的参考依据,研发出的某些化合物已用于临床实验。2008年开始在上海交大担任教授、博士生导师,作为独立PI建立了上海交大第一个、也是目前上海交大闵行校区唯一一个结构生物学实验室。以通讯作者身份在Cell ResearchMolecular MicrobiologySCI期刊上发表8篇论文。获上海市“曙光学者”(2008)、上海市“浦江人才”(2009)、教育部“新世纪优秀人才”(2009)等荣誉。读博士、博士后期间,在Nature(2000年,该论文被Novartis等制药公司作为开发抗癌药物的参考依据)、Science(2000年)、Molecular Cell(2003, 2004年)发表第一作者论文。在交大期间,在Nature Communications (2013, 2017年)、Cell Research(2012年, 该论文被英国皇家学会院士Mariann Bienz选入国际生物医药类论文权威数据库Faculty of 1000)、Nucleic Acids Research(2014年)、Molecular Microbiology(2013, 2014年)、Journal of Molecular Cell Biology(2016年)、Cell Discovery(2015, 2016年)等发表通讯作者或第一作者论文。

    教育经历

    1999.52001.5普林斯顿大学(美国) 化学系博士

    1997.81999.5普林斯顿大学(美国) 化学系硕士

    1992.91997.7中国科学技术大学生物系学士 化学物理学辅修学位

    1997 - 2001 普林斯顿大学 化学系 硕士、博士学位

    工作经历

    2008.6–现在 欧宝app官方网站下载生命科学技术学院教授、博士生导师

    2003.62008.6哈佛大学医学院/波士顿儿童医院(美国) 博士后

    2001.62003.6 Memorial Sloan Kettering癌症研究所/Howard Hughes Medical Institute(美国) 博士后

    荣誉奖励

    获美国Leukemia and Lymphoma Society的Special Fellowship(2005-2008年)、上海市“曙光计划”(2008年)、教育部 “新世纪优秀人才”(2009年)、上海市“浦江人才”(2009年)等荣誉。荣获教育部“高等学校科学研究优秀成果奖(科学技术)”自然科学一等奖(排名第四,2016年)。指导的博士生张振义荣获2014年上海市优秀博士论文。


  • 通过解析酶-底物复合物的晶体结构,辅助以生物化学、生物物理学、微生物学、计算生物学手段,探索微生物代谢途径中关键酶或多亚基酶复合物的底物识别与催化反应机理。例如:

    (1)链霉菌的DNA硫化修饰合成代谢途径

    (2)恶臭假单胞菌的尼古丁分解代谢途径


  • 代表性论文(*:共同通讯作者,#:并列第一作者)

    1.Kulaberoglu Y #, Lin K #, Holder M, Gai Z, Gomez M, Shifa BA, Mavis M, Hua L, Sharif AAD, Lujan C, Smith EJ, Bjedov I, Tapon N, Wu G*, Hergovich A*. Stable MOB1 interaction with Warts/LATS, not Hippo/MST, is essential for development and tissue growth control in Hippo signaling. Nat CommunAccepted. (2017)
    2.Qian T, Wo J, Zhang Y, Song Q, Feng G, Luo R, Lin S*, Wu G*, Chen HF*. Crystal structure of StnA for the biosynthesis of antitumor drug streptonigrin reveals a unique substrate binding mode. Sci Rep7:40254. (2017)
    3.Gai Z, Wang Q, Yang C, Wang L, Deng W, Wu G*. Structural mechanism for the arginine sensing and regulation of CASTOR1 in the mTORC1 signaling pathway. Cell Discov2:16051. (2016)
    4.Gai Z, Chu W, Deng W, Li W, Li H, He A, Nellist M, Wu G*. Structure of the TBC1D7-TSC1 complex reveals that TBC1D7 stabilizes dimerization of the TSC1 C-terminal coiled coil region. J Mol Cell Biol8:411-425. (2016)
    5.Zhao G, Chen C, Xiong W, Gao T, Deng Z, Wu G*, He X*. Structural basis of the substrate preference towards CMP for a thymidylate synthase MilA involved in mildiomycin biosynthesis. Sci Rep6:39675. (2016)
    6.Zhang Z, Akyildiz S, Xiao Y, Gai Z, An Y, Behrens J*, Wu G*. Structures of the APC-ARM domain in complexes with discrete Amer1/WTX fragments reveal that it uses a consensus mode to recognize its binding partners. Cell Discov1:15016. (2015)
    7. Wu G #, Chen D #, Tang H #, Ren Y, Chen Q, Lv Y, Zhang Z, Zhao YL*, Yao Y, Xu P*. Structural insights into the specific recognition of N-heterocycle biodenitrogenation-derived substrates by microbial amide hydrolases. Mol Microbiol91:1009-1021. (2014)
    8.Zhao G #, Wu G #, Zhang Y, Liu G, Han T, Deng Z, He X*. Structure of the N-glycosidase MilB in complex with hydroxymethyl CMP reveals its Arg23 specifically recognizes the substrate and controls its entry. Nucleic Acids Res42:8115-24. (2014)
    9.Zhang Y, Fu L, Qi X, Zhang Z, Xia Y, Jia J, Jiang J, Zhao Y*, Wu G*. Structural insight into the mutual recognition and regulation between Suppressor of Fused and Gli/Ci. Nat Commun4:2608. (2013)
    10.Chen D, Tang H, Lv Y, Zhang Z, Shen K, Lin K, Zhao YL, Wu G*, Xu P*. Structural and computational studies of the maleate isomerase Iso from Pseudomonas putidaS16 reveal a breathing motion wrapping the substrate inside. Mol Microbiol87:1237-1244. (2013)
    11.Zhang Z, Chen L, Gao L, Lin K*, Zhu L, Lu Y, Shi X, Gao Y, Zhou J, Xu P, Zhang J*, Wu G*. Structural basis for the recognition of Asef by Adenomatous Polyposis Coli. Cell Res22:372-386. (2012) 被英国皇家学会院士Marian Bienz选入Faculty of 1000数据库
    其他SCI论文:
    12.Jiang H, Deng R, Yuang X, Shang J, Lu S, Zhao Y, Song K, Liu X, Zhang Q, Chen Y, Chinn YE, Wu G, Li J, Chen G, Yu J*, Zhang J*. Peptidomimetic inhibitors of APC-Asef interaction block colorectal cancer migration. Nat Chem BiolAccepted. (2017)
    13.Zhang K, Wu G, Tang H*, Hu C, Shi T, Xu P*. Structural basis for the transcriptional repressor NicR2 in nicotine degradation from Pseudomonas. Mol Microbiol103:165-180. (2017)
    14.21. Liu G, Zhang Z, Zhao G, Deng Z, Wu G*, He X*. Crystallization and preliminary X-ray analysis of the type IV restriction endonuclease ScoMcrA from Streptomyces coelicolor, which cleaves both Dcm-methylated DNA and phosphorothioated DNA. Acta Crystallogr F71:57-60. (2015)
    15.Jiang Y, Tang H*, Wu G, Xu P*. Functional identification of a novel gene, moaE, for 3-succinoylpyridine degradation in Pseudomonas putidaS16. Sci Rep5:13464. (2015)
    16.Zhang Y, An J, Yang G, Bai A, Zheng B, Lou Z, Wu G, Ye W, Chen HF, Feng Y*, Manco G*. Active site loop conformation regulates promiscuous activity in a lactonase from Geobacillus kaustophilusHTA426. PLoS One10:e0115130. (2015)
    17.Wang H, Zhang Y, Zhang Z, Jin WL*, Wu G*. Purification, crystallization and preliminary X-ray analysis of the inverse F-BAR domain of the human srGAP2 protein. Acta Crystallogr F70:123-126. (2014)
    18.Xie Y, An J, Yang G, Wu G, Zhang Y, Cui L, Feng Y*. Enhanced enzyme kinetic stability by increasing rigidity within the active site. J Biol Chem289:7994-8006. (2014)
    19.Li A, Zhang Y*, Wang C, Wu G*, Wang Z. Purification, molecular cloning, and antimicrobial activity of peptides from the skin secretion of the black-spotted frog, Rana nigromaculata. World J Microbiol Biotechnol29:1941-1949 (2013)
    20.Chen F, Zhang Z, Lin K*, Qian T, Zhang Y, You D, He X, Wang Z, Liang J, Deng Z, Wu G*. Crystal structure of the cysteine desulfurase DndA of Streptomyces lividanswhich is involved in DNA phosphorothioation. PLoS One7:e36635. (2012)
    21.Hu W, Wang C, Liang J, Zhang T, Hu Z, Wang Z, Lan W, Li F, Wu H, Ding J, Wu G, Deng Z, Cao C*. Structural insights into DndE from Escherichia coliB7A involved in DNA phosphorothioation modification. Cell Res22:1203-1206. (2012)
    22.Tang H, Yao Y, Wang L, Yu H, Ren Y, Wu G, Xu P*. Genomic analysis of Pseudomonas putida: genes in a genome island are crucial for nicotine degradation. Sci Rep2:377. (2012)
    23.Li Q, Feng J, Gao C, Li F, Yu C, Meng L, Zhang Z, Ma C*, Gu L*, Wu G, Xu P. Purification and characterization of a flavin reductase from the biodesulfurizing bacterium Mycobacterium goodiiX7B. Process Biochem47:1144-1149. (2012)

  • 1)围绕假单胞菌的尼古丁降解途径,解析了异构酶Iso与底物马来酸的复合物结构,Iso把马来酸完全包裹在内部,其两段loops有一开一合的运动,调节底物进入与产物释放(Mol Microbiol, 2013)。解析了脱甲酰基酶Nfo与脱氨基酶Ami的结构,揭示了NfoAmi有着针对各自底物量身定制的活性位点,不能交换底物交叉反应的机制。阐明了两类脱氨基酶选择性识别含羧基与含芳香环底物的机制(Mol Microbiol, 2014)。解析了转录调节蛋白NicR2与诱导物HSP的复合物结构,阐明了NicR2特异性识别HSP的机理(Mol Microbiol, 2017)。

    2)围绕细菌的DNA硫化修饰途径,解析了半胱氨酸脱硫酶DndA与辅基磷酸吡哆醛的复合物结构,揭示了DndA的活性位点与底物结合位点有长达16埃的距离,指出DndA在催化过程中发生较大的构象变化(PLoS One, 2012)。与曹春阳教授合作解析了DndE蛋白结构(Acta Crystallogr F, 2011Cell Res, 2012)。

    3)针对链霉菌的米多霉素合成途径,解析了糖苷水解酶MilB与底物羟甲基胞苷酸的复合物结构,揭示其精氨酸23采取不同构象,将底物封锁在活性位点口袋内,以催化底物糖苷键水解(Nucleic Acids Res, 2014)。解析了胞苷酸羟甲基化酶MilA与底物胞苷酸的复合物结构,阐明了MilA识别胞苷酸而非脱氧胞苷酸的机理(Zhao et al., Sci Rep, 2016)。针对链霉菌的链黑菌素合成途径,阐明了甲酯水解酶StnA识别底物STM的结构机理(Qian et al., Sci Rep, 2017)。

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