Towards investigation of the inhibitor-recognition mechanisms of drug-target proteins by neutron crystallography

• Published in: Acta crystallographica. Section D, Biological crystallography. Vol. 66; no. 11; pp. 1126 - 1130
• Main Authors: Kuroki, Ryota, Okazaki, Nobuo, Adachi, Motoyasu, Ohhara, Takashi, Kurihara, Kazuo, Tamada, Taro
• Format: Journal Article
• Language: English
• Published: 5 Abbey Square, Chester, Cheshire CH1 2HU, England International Union of Crystallography 01.11.2010
• Subjects: Animals; catalytic mechanism; Crystallography; Crystallography, X-Ray; Diffractometers; Drug Design; drug targets; Elastase; Enzyme Inhibitors - metabolism; Enzymes; HIV Protease - chemistry; HIV Protease - metabolism; Human immunodeficiency virus; Humans; inhibitor recognition; Inhibitors; Models, Molecular; Neutron Diffraction; Neutrons; Pancreatic Elastase - chemistry; Pancreatic Elastase - metabolism; Protein Conformation; Proteins; Recognition; Swine
• ISSN: 1399-0047; 0907-4449; 1399-0047
• DOI: 10.1107/S0907444910034967

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.