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Kuroki, Ryota; Tamada, Taro; Kurihara, Kazuo; Ohara, Takashi; Adachi, Motoyasu
Yakugaku Zasshi, 130(5), p.657 - 664, 2010/05
Times Cited Count：0 Percentile：0.02(Pharmacology & Pharmacy)Crystallography enables us to obtain accurate atomic positions within proteins. High resolution X-ray crystallography provides information for most of the atoms comprising a protein, with the exception of hydrogens. Neutron diffraction data can provide information of the location of hydrogen atoms to the structural information determined by X-ray crystallography. Here, we show the recent result of the structural determination of drug-target proteins, porcine pancreatic elastase and human immuno-deficiency virus type-1 protease by both X-ray and neutron diffraction. The structure of porcine pancreatic elastase with its potent inhibitor was determined at room temperature to 1.2 
resolution by X-ray diffraction and 1.65 resolution by neutron diffraction. The structure of HIV-PR with its potent inhibitor was also determined to 1.4 resolution by X-ray diffraction and 1.9 resolution by neutron diffraction. Ultra-high resolution structures of both proteins (0.94 and 0.93 , respectively) were also determined by X-ray diffraction at 100 K. The ionization state and the location of hydrogen atoms of the catalytic residue in these enzymes were determined by neutron diffraction. Furthermore, collaborative use of both X-ray and neutron to identify the location of ambiguous hydrogen atoms will be shown.
Tanaka, Ichiro*; Kusaka, Katsuhiro*; Hosoya, Takaaki*; Ohara, Takashi*; Kurihara, Kazuo; Niimura, Nobuo*
Yakugaku Zasshi, 130(5), p.665 - 670, 2010/05
Times Cited Count：0 Percentile：0.02(Pharmacology & Pharmacy)Ibaraki Prefectural Government together with Ibaraki University and Japan Atomic Energy Agency (JAEA) has almost finished constructing a time-of-flight (TOF) neutron diffractometer for biological macromolecules for industrial use at J-PARC, IBARAKI Biological Crystal Diffractometer (iBIX). Since 2009, Ibaraki University has been asked to operate this machine in order for users to do experiments by Ibaraki Prefecture. The diffractometer is designed to cover sample crystals which have their cell edges up to around 150 . It is expected to measure more than 100 samples per year if they have 2 mm
in crystal volume, and to measure even around 0.1 mm in crystal volume of biological samples. The efficiency of iBIX is also expected about 100 times larger than those of the present high performance diffractometers at JRR-3 in JAEA when 1MW power realizes in J-PARC. Since December 2008, iBIX has been open to users and several proteins and organic compounds were tested under 20 kW proton power of J-PARC. It was found that one of their proteins was diffracted up to 1.4 in d-spacing, which was nearly comparable resolution to that of BIX-3 in JRR-3 when used the same crystal as at iBIX for reasonable exposure time. In May 2009, 14 detector units were set up. By the end of fiscal year 2009, the basic part of data reduction software will be finished and an equipment blowing low temperature gas to the sample will be installed with the cooperation of JAEA.
