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 drugtarget proteins, porcine pancreatic elastase and human immuno-defficiency 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 Å resolution by X-ray diffraction and 1.65 Å resolution by neutron diffraction. The structure of HIV-PR with its potent inhibitor was also determined to 0.93 Å resolution by X-ray diffraction and 1.9 Å 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. © 2010 The Pharmaceutical Society of Japan.