2001 Fiscal Year Final Research Report Summary
Drug design for transcription factors
| Project/Area Number |
11358012
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Biophysics
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| Research Institution | Yokohama City University |
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Principal Investigator |
NISHIMURA Yoshifumi Graduate School of Integrated Science, Professor, 大学院・総合理学研究科, 教授 (70107390)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Ichirou AJINOMOTO, Co, LTd, Analytical Chemistry Laboratories Central Research Laborstories, Senior Researcher, 中央研究所・分析研究部, 主席研究員
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| Project Period (FY) |
1999 – 2001
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| Keywords | transcription tactors / DNA-binding proteins / drug / flow-type automated NMR / double-strand DNA chip / telomeres / TRF / hRapl |
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| Research Abstract |
We have developed new technologies to analyze DNA-binding protein function and the interaction between proteins and other small molecules. New approach under development include a double-stranded DNA chip to detect DNA-binding specificities of proteins and a Protein Recycling Flow NMR system that will allow for faster screening of compounds that interact with proteins, while using much smaller amounts of the protein being screened.
By using the newly developed double-stranded DNA chip we have detected rapidly the sequence specificity of human TRF1 that binds double stranded telomeric DNA. Many double-stranded DNA with different sequences were chipped on a glass slide and then hTRF1 was spotted on the glass slide. The intensities of the fluorescence labeled DNA indicate the sequence specificities of hTRF1. The each intensity of a specific DNA sequence bound hTRF1 is well correlated to the binding dissociation constant of hTRF1 for each DNA sequence examined by using BIACORE. By using BIACORE it takes seven days to analyze the binding constants of hTRF1 for seven different sequences, while by using our new double-stranded DNA chip it takes half an hour.
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Research Products
(24 results)
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[Publications] Nagadoi, A., Nakazawa, K.Uda, H, Okuno, K., Maekawa, T., Ishii, S., Nishimura, Y: "Solution structure of the transactivation domain of ATF-2 comprising a zinc finger-like subdomain and a flexible subdomain"J.Mol.Biol. 287. 593-607 (1999)
Description
「研究成果報告書概要(和文)」より
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[Publications] Yokoyama, S., Matsuo, Y., Hirota, H., Kigawa, T., Shirouzu, M., Kuroda, Y., Kurumizaka, H., Kawaguchi, S., Ito, Y., Shibata, T., Kainosho, M., Nishimura, Y., Inoue, Y., Kuramitsu, S.: "Structural genomics projects in Japan"Progress in Biophysics & Molecular Biology. 73. 363-376 (2000)
Description
「研究成果報告書概要(和文)」より
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[Publications] Hanaoka, S., Nagadoi, A., Yoshimura, S., Aimoto, S., Li, B., de Lange, T., Nishimura, Y.: "NMR structure of the hRap1 Myb motif reveals a canonical three helix bundle lacking the positive surface charge typical of Myb DNA binding domains"J.Mol.Biol.. 312. 167-175 (2001)
Description
「研究成果報告書概要(和文)」より
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[Publications] Nishikawa, T., Okumura, M., Nagadoi, A., Konig, P., Rhodes, D., Nishimura, Y.: "Solution Structure of a Telomeric DNA Complex of Human TRF1"Structure. 9. 1237-1251 (2001)
Description
「研究成果報告書概要(和文)」より
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[Publications] Nagadoi,A., Nakazawa,K., Uda,H., Okuno,K., Maekawa,T., Ishii,S., and Nishimura,Y.: "Solution structure of the transactivation domain of ATF-2 comprising a zinc finger-like subdomain and a flexible subdomain"J. Mol. Biol.. 287. 593-607 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Okuda,M., Watanabe,Y., Okamura,H., Hanaoka,F., Ohkuma,Y., and Nishimura,Y.: "Structure of the Central Core Domain of TFIIEβ with a Novel Double-stranded DNA-binding Surface"BMBO J.. 19. 1346-1356 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yokoyama,S., Matsuo,Y., Hirota,H., Kigawa,T., Shirouzu,M., Kuroda,Y., Kurumizaka,H., Kawaguchi,S., Ito,Y., Shibata,T., Kainosho,M., Nishimura,Y., Inoue,Y., Kuramitsu,S.: "Structural genomics projects in Japan. Biophysics & Molecular"Biology. 73. 363-376 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hanaoka,S., Nagadoi,A., Yoshimura,S., Aimoto,S., Li,B., de Lange,T., and Nishimura,Y.: "NMR structure of the hRapl Myb motif reveals a canonical three helix bundle lacking the positive surface charge typical of Myb DNA binding domains"J. Mol. Biol.. 312. 167-175 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Nishikawa,T., Okamura,H., Nagadoi,A., Konig,P., Rhodes,D., and Nishimura,Y.: "Solution Structure of a Telomeric DNA Complex of Human TRF1"Structure. 9. 1237-1251 (2001)
Description
「研究成果報告書概要(欧文)」より
