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Sugimoto, Jun; Sakamoto, Ryuichi; Kushita, Kohei; Arai, Nobuyoshi; Hattori, Takamitsu; Matsuda, Kenji; Ikuta, Yuko; Sato, Koichi
Transactions of NESTet 2008 (CD-ROM), 6 Pages, 2008/05
Nuclear human resources development (HRD) in Japan has been identified as one of the most important issues these years in nuclear society, mostly due to the decrease of nuclear engineers in industries and students in universities, and to the difficulties of technical transfers. Nuclear Technology and Education Center (NuTEC) at Japan Atomic Energy Agency (JAEA) aims at comprehensive nuclear education and training activities, which cover (1) education and training for domestic nuclear engineers, (2) cooperation with universities and (3) international cooperation. The main feature of NuTEC's training programs is that the curricula places emphasis on the laboratory exercise with well-equipped training facilities and expertise of lecturers mostly from JAEA. The wide spectrum of cooperative activities have been pursued with universities, which includes newly developed remote-education system, and also with international organizations, such as with FNCA countries and IAEA.
Adachi, Motoyasu; Arai, Shigeki; Matsumoto, Fumiko; Kuroki, Ryota; Hatanaka, Takaaki*; Ito, Yuji*; Hidaka, Koshi*; Tsuda, Yuko*; Kiso, Yoshiaki*
no journal, ,
HIV protease is known as a drug target protein. To compare interactions between HIVPR and inhibitors, single-chained HIVPR linked by a disulfide bond was designed as N98C mutant. Both WT N98C and A17 N98C mutants were expressed as inclusion body and refolded by dilution method. The yield of the purified enzymes was similar to that of WT. We will report the results of interactions between inhibitors and WT N98C and A17 N98C mutants by physicochemical and crystal structure analyses.
Hidaka, Koshi*; Adachi, Motoyasu; Kuroki, Ryota; Tokai, Satoko*; Akaji, Kenichi*; Tsuda, Yuko*; Kiso, Yoshiaki*
no journal, ,
In the HIV protease inhibitor study, we faced on a problem of much difference in activity of a compound with 2,6-dimethylphenoxyacetyl moiety against the enzyme and the virus. The protease inhibitory potency was plateau because of the limited structural modifications. Therefore, we shifted to modify the property such as reduction of the hydrophobicity. During the struggles, amino substitution succeeded in improving the water solubility to enhance the anti-HIV activity and with the sustained protease inhibitory activity. This result stimulated us to modify the Apns-containing inhibitors for the development of therapeutic drug and to utilize them as aspartic proteases probes.
Adachi, Motoyasu; Hatanaka, Takaaki*; Ito, Yuji*; Hidaka, Koshi*; Tsuda, Yuko*; Kiso, Yoshiaki*; Kuroki, Ryota
no journal, ,
HIV protease is known as a drug target protein. It is important to clear relationship between structural data and kinetic and physicochemical parameters for drug design. We prepared single-chained enzyme linked by two amino acids and cross-liked enzyme bridged by disulfide bond. The two single-chained enzymes were expressed as inclusion body and refolded by dilution method. The purified enzyme complexed with inhibitor KNI-272 was crystallized, and solved the crystal structures. The designed sc- and cl-HIV-PR will be useful for evaluate the affinity of newly designed inhibitors from kinetic and thermodynamic point of view. Finally, we also report the results of analysis in affinity of inhibitors by surface plasmon resonance.
Adachi, Motoyasu; Shimizu, Rumi; Kuroki, Ryota; Moriya, Keisuke*; Kidokoro, Shunichi*; Hidaka, Koshi*; Tsuda, Yuko*; Kiso, Yoshiaki*
no journal, ,
Human immune deficiency virus protease-I (HIV-PR) is one of the important drug target proteins for the acquired immune deficiency syndrome. In this study, we designed the two single chain derivatives of wild-type and A17 type HIV-PRs in which the catalytic residue of Asp25 was placed with Asn25 to inactivate the enzyme. The tertiary structure of sc-HIV-PR of wild-type and A17 type were determined by X-ray crystallography to 1.1 and 1.5 
resolution, respectively. The both complex structures showed that Asn25 forms hydrogen bond with carbonyl group of inhibitor.