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Kurihara, Kazuo; Tamada, Taro; Ohara, Takashi; Kuroki, Ryota
no journal, ,
Ohara, Takashi; Adachi, Motoyasu; Tamada, Taro; Kuroki, Ryota; Kondo, Hidemasa*; Nishimiya, Yoshiyuki*; Tsuda, Sakae*
no journal, ,
no abstracts in English
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.
Okazaki, Nobuo; Ohara, Takashi; Umino, Hisao*; Chatake, Toshiyuki*; Kurihara, Kazuo; Cachau, R. E.*; Blaber, M.*; Niimura, Nobuo*; Kuroki, Ryota
no journal, ,
In protein molecules, key energetic contributors are solvation, desolvation and hydrogen bonding. They contribute protein folding, dynamics and molecular recognition. As a result, more elaborate studies of hydrogen atoms will be great help to recognize protein structures and obtain new findings of them. However, we do not have system which dedicated to characterization and analysis of hydrogen bonding. Therefore, we have developed a database for hydrogen and hydration water molecules. That database named Hydrogen and Hydration Database for Biomolecules (HHDB). Hydrogen bond data stored to HHDB use hydrogen atom coordinates determined directly by neutron diffraction and certain extremely high resolution X-ray diffraction. HHDB provides graphical user interface, users can use it through web browser. HHDB can visualize hydrogen atom positions in protein and solvent, and hydrogen bonding interactions. Fig. 1 shows HHDB plot example. In this plot, hydrogen atom is placed at the origin, and each point represents hydrogen bond distance and angle. We are improving the web user interfaces and the performance for usability.
Tamada, Taro; Kinoshita, Takayoshi*; Ohara, Takashi; Kurihara, Kazuo; Imai, Keisuke*; Kuroki, Ryota; Tada, Toshiji*
no journal, ,
Porcine pancreatic elastase (PPE) is a serine protease classified in the chymotrypsin family. We determined two crystal structures of PPE in complex with peptidic inhibitor FR130180, which mimics the tetrahedral transition intermediate. One is the structure determined using 1.65 resolution neutron diffraction in the combination with 1.20 resolution X-ray diffraction data obtained using the same crystal. The other is the sub-angstrom X-ray structure determined to 0.94 resolution. The structural features obtained from neutron diffraction and X-ray diffraction were compared to understand the detailed scheme of interaction between PPE and its inhibitor. From the observation of hydrogen atom located between the active site His57 and Asp102 by neutron and high resolution X-ray diffraction experiment, it is revealed that the interaction is not a low barrier hydrogen bond, but a short ionic hydrogen bond. Moreover, using neutron diffraction data we show that the hydroxyl group of inhibitor FR13080 bound within the "oxy-anion hole" exhibits an oxy-anion-like tetrahedral intermediate.