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Adachi, Motoyasu; Ohara, Takashi; Kurihara, Kazuo; Tamada, Taro; Honjo, Eijiro; Okazaki, Nobuo; Arai, Shigeki; Shoyama, Yoshinari; Kimura, Kaname*; Matsumura, Hiroyoshi*; et al.
Proceedings of the National Academy of Sciences of the United States of America, 106(12), p.4641 - 4646, 2009/03
Times Cited Count：111 Percentile：90.72(Multidisciplinary Sciences)To further understand the catalytic mechanism and inhibitor recognition of HIV-1 protease, we need to determine the locations of key hydrogen atoms in the catalytic aspartates Asp25 and Asp125. The structure of HIV-1 protease in complex with transition-state analog KNI-272 was determined by combined neutron crystallography at 1.9 
resolution and X-ray crystallography at 1.4 resolution. The resulting structural data shows that the catalytic residue Asp25 is protonated and that Asp125 is deprotonated. The proton on Asp25 makes a hydrogen bond with the carbonyl group of the allophenylnorstatine group in KNI-272. The deprotonated Asp125 bonds to the hydroxyl proton of Apns. The results provide direct experimental evidence for proposed aspects of the catalytic mechanism of HIV-1 protease; and can therefore contribute substantially to the development of specific inhibitors for therapeutic application.
Matsukawa, Makoto; Kikuchi, Mitsuru; Fujii, Tsuneyuki; Fujita, Takaaki; Hayashi, Takao; Higashijima, Satoru; Hosogane, Nobuyuki; Ikeda, Yoshitaka; Ide, Shunsuke; Ishida, Shinichi; et al.
Fusion Engineering and Design, 83(7-9), p.795 - 803, 2008/12
Times Cited Count：17 Percentile：72.86(Nuclear Science & Technology)no abstracts in English
Ninomiya, Hiromasa; Akiba, Masato; Fujii, Tsuneyuki; Fujita, Takaaki; Fujiwara, Masami*; Hamamatsu, Kiyotaka; Hayashi, Nobuhiko; Hosogane, Nobuyuki; Ikeda, Yoshitaka; Inoue, Nobuyuki; et al.
Journal of the Korean Physical Society, 49, p.S428 - S432, 2006/12
To contribute DEMO and ITER, the design to modify the present JT-60U into superconducting coil machine, named National Centralized Tokamak (NCT), is being progressed under nationwide collaborations in Japan. Mission, design and strategy of this NCT program is summarized.
Kikuchi, Mitsuru; Tamai, Hiroshi; Matsukawa, Makoto; Fujita, Takaaki; Takase, Yuichi*; Sakurai, Shinji; Kizu, Kaname; Tsuchiya, Katsuhiko; Kurita, Genichi; Morioka, Atsuhiko; et al.
Nuclear Fusion, 46(3), p.S29 - S38, 2006/03
Times Cited Count：13 Percentile：41.76(Physics, Fluids & Plasmas)The National Centralized Tokamak (NCT) facility program is a domestic research program for advanced tokamak research to succeed JT-60U incorporating Japanese university accomplishments. The mission of NCT is to establish high beta steady-state operation for DEMO and to contribute to ITER. The machine flexibility and mobility is pursued in aspect ratio and shape controllability, feedback control of resistive wall modes, wide current and pressure profile control capability for the demonstration of the high-b steady state.
Tsuchiya, Katsuhiko; Akiba, Masato; Azechi, Hiroshi*; Fujii, Tsuneyuki; Fujita, Takaaki; Fujiwara, Masami*; Hamamatsu, Kiyotaka; Hashizume, Hidetoshi*; Hayashi, Nobuhiko; Horiike, Hiroshi*; et al.
Fusion Engineering and Design, 81(8-14), p.1599 - 1605, 2006/02
Times Cited Count：1 Percentile：9.98(Nuclear Science & Technology)no abstracts in English
plasma operationTamai, Hiroshi; Akiba, Masato; Azechi, Hiroshi*; Fujita, Takaaki; Hamamatsu, Kiyotaka; Hashizume, Hidetoshi*; Hayashi, Nobuhiko; Horiike, Hiroshi*; Hosogane, Nobuyuki; Ichimura, Makoto*; et al.
Nuclear Fusion, 45(12), p.1676 - 1683, 2005/12
Times Cited Count：15 Percentile：45.53(Physics, Fluids & Plasmas)Design studies are shown on the National Centralized Tokamak facility. The machine design is carried out to investigate the capability for the flexibility in aspect ratio and shape controllability for the demonstration of the high-beta steady state operation with nation-wide collaboration, in parallel with ITER towards DEMO. Two designs are proposed and assessed with respect to the physics requirements such as confinement, stability, current drive, divertor, and energetic particle confinement. The operation range in the aspect ratio and the plasma shape is widely enhanced in consistent with the sufficient divertor pumping. Evaluations of the plasma performance towards the determination of machine design are presented.
Adachi, Motoyasu; Kimura, Kaname*; Kuroki, Ryota
no journal, ,
Cytochrome P450 3A4 is the most important enzyme involving metabolism of drag xenobiotics. The crystallography of cytochrome P450 3A4 is a pilot study for Shinyaku-sohsei society. Cytochrome P450 3A4 was expressed by using E. coli system. However, the expressed protein was insolble protein, suggesting the obtained protein is not folded as native protein. Here, I suggest plans to solve the problem.
Adachi, Motoyasu; Ohara, Takashi; Kurihara, Kazuo; Tamada, Taro; Honjo, Eijiro; Okazaki, Nobuo; Arai, Shigeki; Shoyama, Yoshinari; Kimura, Kaname*; Matsumura, Hiroyoshi*; et al.
no journal, ,
HIV-1 protease is a dimeric aspartic protease that cleaves the nascent polyproteins of HIV-1 and plays an essential role in viral replication. To further understand the catalytic mechanism of HIV-1 protease, we have determined the crystal structure of HIV-1 protease in complex with a transition state mimetic tripeptide inhibitor, KNI-272 to 1.9 resolution by neutron crystallography in combination with 1.4 resolution X-ray diffraction data. Our results indicates that the carbonyl group of allophenylnorstatine in KNI-272 forms a significant hydrogen bond with protonated Asp 25, and the hydrogen atom from the hydroxyl group of Apns forms a remarkable hydrogen bond with the deprotonated Asp125. These results show direct evidence that Asp25 provides a proton to carbonyl group of substrate and Asp125 contributes to activate the attacking water molecule as a nucleophile.
