Structures of drug-target proteins determined by both X-ray and neutron diffraction

Kuroki, Ryota

X-ray and neutron crystallography enables us to obtain accurate atomic positions within proteins. The structure of porcine pancreatic elastase (PPE) with its potent inhibitor (FR130180) was determined to 0.94 resolution by X-ray diffraction and 1.75 resolution by neutron diffraction. It was found that there are two characteristic hydrogen bonding interactions in which hydrogen atoms were confirmed. One is located between a catalytic aspartate and histidine, another is involved in the inhibitor recognition site. The structure of HIV-PR with its potent inhibitor (KNI-272) was also determined to 0.93 resolution by X-ray diffraction and 2.3 resolution by neutron diffraction. The ionization state of the catalytic residues were clarified to show that Asp125 is protonated and Asp25 is deprotonated. The ionization state and the location of hydrogen atoms of the catalytic residue in HIV-PR were firstly determined by neutron diffraction.