核糖核酸酶Ⅲ（RNaseⅢ）家族是一類識別特定序列對雙鏈RNA進行切割的內(nèi)切酶,，切割后一般產(chǎn)物3'末端會帶有兩個堿基的粘性末端,。目前RNaseⅢ家族研究得最多的是在RNA干擾途徑中起重要作用的Dicer酶,，它負責切割雙鏈雙鏈RNA后產(chǎn)生小干擾RNA,；而結構較簡單的細菌RNaseⅢ則是作為這一類酶的介紹典型,。
來自美國國立健康研究院(NIH)癌癥研究中心的華人學者吉新華（音譯：Ji Xinhua）帶領的研究小組,，第一次解開了RNaseⅢ與產(chǎn)物結合復合物的晶體結構,，文章發(fā)表在1月26日的Cell雜志上,。吉新華是RNA結構領域的權威。
研究人員利用經(jīng)過突變后酶活性有所降低的RNaseⅢ進行研究,，對酶進行催化的活性部位的三級結構進行了研究,，從而進一步解釋了RNaseⅢ進行切割時的機制。研究發(fā)現(xiàn),，在蛋白中7個殘基的接頭（linker）幫助蛋白與RNA直接的識別,。在RNaseⅢ中確定了四類的RNA結合基元（motif），在dsRNA中確定有三個相互作用盒,。保守的氨基酸殘基和二價陽離子負責斷裂鍵,。對這些水解RNA機制的了解可以進一步推廣到其它RNaseⅢ家族的成員中。
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: [email protected]
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]
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