Towards investigation of the inhibitor-recognition mechanisms of drug-target proteins by neutron crystallography.
It is generally known that enzymes represent important drug-target proteins. Elucidation of the catalytic function and the molecular-recognition mechanisms of enzymes provides important information for structure-based drug design. Neutron crystallography provides accurate information on the locations of H atoms that are essential in enzymatic function and molecular recognition. Recent examples are described of the structure determination of the drug-target proteins human immunodeficiency virus protease and porcine pancreatic elastase in complex with transition-state analogue inhibitors using the neutron diffractometers for biological crystallography (BIX-3 and BIX-4) installed at the JRR-3 research reactor.
Molecular Biology Research Center, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 2-4 Shirakata-shirane, Tokai, Ibaraki 319-1195, Japan. kuroki.ryota@jaea.go.jp
Ryota
R
Kuroki
Nobuo
N
Okazaki
Motoyasu
M
Adachi
Takashi
T
Ohhara
Kazuo
K
Kurihara
Taro
T
Tamada
D000818:Animals; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000378:metabolism*; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D033363:Neutron Diffraction; D009502:Neutrons; D010196:Pancreatic Elastase / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D013552:Swine
D004791:Enzyme Inhibitors; D010196:Pancreatic Elastase; D016333:HIV Protease