title: [Collaborative use of neutron and X-ray for determination of drug target proteins].
abstract: 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, and is complementary 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 to 0.94 A resolution by X-ray diffraction and 1.65 A resolution by neutron diffraction. The structure of HIV-PR with its potent inhibitor was also determined to 0.93 A resolution by X-ray diffraction and 1.9 A resolution by neutron diffraction. 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.
authors.affiliation: Japan Atomic Energy Agency, Ibaraki, Japan. kuroki.ryota@jaea.go.jp
authors.forename: Ryota
authors.initials: R
authors.lastname: Kuroki
authors.forename: Taro
authors.initials: T
authors.lastname: Tamada
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kurihara
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohhara
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Adachi
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D015195:Drug Design; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D006859:Hydrogen; D033363:Neutron Diffraction / Q000295:instrumentation / Q000379:methods; D009502:Neutrons; D010196:Pancreatic Elastase / Q000737:chemistry*; D010447:Peptide Hydrolases / Q000737:chemistry*; D011480:Protease Inhibitors / Q000737:chemistry*; D011487:Protein Conformation; D013552:Swine; D014961:X-Ray Diffraction / Q000295:instrumentation / Q000379:methods; D014965:X-Rays
chemical_list: D011480:Protease Inhibitors; D006859:Hydrogen; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase