核糖核酸酶Ⅲ（RNaseⅢ）家族是一类识别特定序列对双链RNA进行切割的内切酶，切割后一般产物3'末端会带有两个碱基的粘性末端。目前RNaseⅢ家族研究得最多的是在RNA干扰途径中起重要作用的Dicer酶，它负责切割双链双链RNA后产生小干扰RNA；而结构较简单的细菌RNaseⅢ则是作为这一类酶的介绍典型。
来自美国国立健康研究院(NIH)癌症研究中心的华人学者吉新华（音译：Ji Xinhua）带领的研究小组，第一次解开了RNaseⅢ与产物结合复合物的晶体结构，文章发表在1月26日的Cell杂志上。吉新华是RNA结构领域的权威。
研究人员利用经过突变后酶活性有所降低的RNaseⅢ进行研究，对酶进行催化的活性部位的三级结构进行了研究，从而进一步解释了RNaseⅢ进行切割时的机制。研究发现，在蛋白中7个残基的接头（linker）帮助蛋白与RNA直接的识别。在RNaseⅢ中确定了四类的RNA结合基元（motif），在dsRNA中确定有三个相互作用盒。保守的氨基酸残基和二价阳离子负责断裂键。对这些水解RNA机制的了解可以进一步推广到其它RNaseⅢ家族的成员中。
Chief, Biomolecular Structure Section
Macromolecular Crystallography Laboratory
National Cancer Institute
National Cancer Institute at Frederick
P.O. Box B, Building 539, Room 124
Frederick, MD 21702-1201
Phone: 301-846-5035
Fax: 301-846-6073
E-mail: jix@ncifcrf.gov
Dr. Ji obtained his Ph.D. from the University of Oklahoma in 1990 and received postdoctoral training at the University of Maryland Biotechnology Institute, where he became a Research Assistant Professor before joining the National Cancer Institute (NCI). At NCI-Frederick, Dr. Ji established his laboratory in the ABL-Basic Research Program in 1995, moved to the Center for Cancer Research as a Section Chief in 1999, and in 2001 gained tenure as an NIH Senior Investigator.
Patents
1. "O2-aryl substituted diazeniumdiolates and use thereof," J. Saavedra, L. Keefer, A. Srinivasan, C. Bogdan, W. Rice, and X. Ji, Australia Patent Number 733590. 2001.
2. "O2-arylated or O2-glycosylated 1-substituted diazen-1-ium-1,2-diolates and O2-substituted 1-[(2-carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolates," J.E. Saavedra, L.K. Keefer, A. Srinivasan, W.G. Rice, X. Ji, and C. Bogdan, US Patent Number 6610660. 2003.
3. "O2-arylated or O2-glycosylated 1-substituted diazen-1-ium-1,2-diolates and O2-substituted 1-[(2-carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolates," J.E. Saavedra, L.K. Keefer, A. Srinivasan, C. Bogdan, W.G. Rice, and X. Ji, European Patent Number EP 0 929 538 B1. 2004.
Recent Publications
79. “Crystal structure of the broadly cross-reactive HIV-1-neutralizing Fab X5 and fine mapping of its epitope,” R. Darbha, S. Phogat, A.F. Labrijn, Y. Shu, Y. Gu, M. Andrykovitch, M.-Y. Zhang, R. Pantophlet, L. Martin, C. Vita, D.R. Burton, D.S. Dimitrov, and X. Ji, Biochemistry (Accelerated Publications) 43, 1410-1417 (2004). [Abstract]
80. “Essential roles of a dynamic loop in the catalysis of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase,” J. Blaszczyk, Y. Li, Y. Wu, G. Shi, X. Ji, and H. Yan, Biochemistry 43, 1469-1477 (2004). [Abstract]
81. “Non-catalytic assembly of ribonuclease III with double-stranded RNA,” J. Blaszczyk, J. Gan, J.E. Tropea, D.L. Court, D.S. Waugh, and X. Ji, Structure 12, 457-466 (2004). [Abstract]
82. “Reaction trajectory of pyrophosphoryl transfer catalyzed by a 6-hydroxymethyl-7,8- dihydropterin pyrophosphokinase,” J. Blaszczyk, G. Shi, Y. Li, H. Yan, and X. Ji, Structure 12, 467-475 (2004). [Abstract]
83. "Tumor cell responses to a novel glutathione S-transferase-activated nitric oxide releasing prodrug," V.J. Findlay, D.M. Townsend, J.E. Saavedra, G.S. Buzard, M.L. Citro, L.K. Keefer, X. Ji, and K.D. Tew, Mol. Pharmacol. 65, 1070-1079 (2004).[Abstract]
84. "Impact of antibody framework residue VH-71 on the stability of a humanised anti-MUC1 scFv and derived immunoenzyme," J. Krauss, M.A.E. Arndt, Z. Zhu, D. L. Newton, B.K. Vu, V. Choudhry, R. Darbha, X. Ji, N.S. Courtenay-Luck, M.P. Deonarain, J. Richards, and S.M. Rybak, Br. J. Cancer, 90, 1863-1870 (2004). [Abstract]
85. "Structural Basis for Catalytic Differences between Alpha Class Human Glutathione Transferases hGSTA1-1 and hGSTA2-2 for Glutathione Conjugation of Environmental Carcinogen Benzo[a]pyrene-7,8-diol-9,10-epoxide," S. V. Singh, V. Varma, P. Zimniak, S. K. Srivastava, S.W. Marynowski, S. Amin, and X. Ji, Biochemistry, 43, 9708-9715 (2004). [Abstract]
86. "Crystal structure of human glutathione S-transferase A3-3 and mechanistic implications for its high steroid isomerase activity," Y. Gu, A. Pal, S.-S. Pan, S.V. Singh, and X. Ji, Biochemistry 43, 15673-15679 (2004). [Abstract]
87. "Structural basis for the function of stringent starvation protein A as a transcription factor," A.-M. Hansen, Y. Gu, M. Li, M. Andrykovitch, D.S. Waugh, D.J. Jin, and X. Ji, J. Biol. Chem. 208, 17380-17391 (2005). [Abstract]
88. "Is the Critical Role of Loop 3 of Escherichia coli 6-Hydroxymethyl-7,8-dihydropterin Pyrophosphokinase in Catalysis Due to Loop-3 Residues Arginine-84 and Tryptophan-89? Site-directed Mutagenesis, Biochemical, and Crystallographic Studies," Y. Li, J. Blaszczyk, Y. Wu, G. Shi, X. Ji, and H. Yan, Biochemistry 44, 8590-8599 (2005). [Abstract]
89. "Intermediate states of ribonuclease III in complex with double-stransed RNA," J. Gan, J.E. Tropea, B.P. Austin, D.L. Court, D.S. Waugh, and X. Ji, Structure 13, 1435-1442 (2005). [Abstract]
90. "A glutathione S-transferase π activated pro-drug causes kinase activation concurrent with S-glutathionylation of proteins,” D.M. Townsend, V.J. Findlay, F. Fazilev, M. Ogle, J. Fraser, J. Saavedra, X. Ji, L. Keefer, and K.D. Tew, Molecular Pharmacology 69, 501-508 (2006, online 11/2005). [Abstract]
91. “Structural insight into the mechanism of double-stranded RNA processing by ribonuclease III,” J. Gan, J.E. Tropea, B.P. Austin, D.L. Court, D.S. Waugh, and X. Ji, Cell 124, 355-366 (2006). [Abstract]
92. “PABA/NO as an anticancer lead: Analogue synthesis, structural revision, solution chemistry, reactivity toward glutathione, and in vitro activity,” J.E. Saavedra, A. Srinivasan, G.S. Buzard, K.M. Davies, D.J. Waterhouse, K. Inami, T.C. Wilde, M.L. Citro, M. Cuellar, J.R. Deschamps, D. Parrish, P.J. Sharmi, V.J. Findlay, D.M. Townsend, K.D. Tew, S.V. Singh, L. Jia, X. Ji, and L.K. Keefer, J. Med. Chem. (online 01/2006). [Abstract]
93. “Structural mimicry of CD4 by a cross-reactive HIV-1 neutralizing antibody with CDR-H2 and H3 containing unique motifs,” P.Prabakaran, J. Gan, Y.-Q. Wu, M.-Y. Zhang, D.S. Dimitrov, and X. Ji, J. Mol. Biol. (online 01/2006). [Abstract]
吉新华的主页
