Re-evaluation of protein neutron crystallography with and without X-ray/neutron joint refinement

IUCrJ. 2022 Apr 8;9(Pt 3):342-348. doi: 10.1107/S2052252522003657. eCollection 2022 May 1.

Abstract

Protein neutron crystallography is a powerful technique to determine the positions of H atoms, providing crucial biochemical information such as the protonation states of catalytic groups and the geometry of hydrogen bonds. Recently, the crystal structure of a bacterial copper amine oxidase was determined by joint refinement using X-ray and neutron diffraction data sets at resolutions of 1.14 and 1.72 Å, respectively [Murakawa et al. (2020 ▸). Proc. Natl Acad. Sci. USA, 117, 10818-10824]. While joint refinement is effective for the determination of the accurate positions of heavy atoms on the basis of the electron density, the structural information on light atoms (hydrogen and deuterium) derived from the neutron diffraction data might be affected by the X-ray data. To unravel the information included in the neutron diffraction data, the structure determination was conducted again using only the neutron diffraction data at 1.72 Å resolution and the results were compared with those obtained in the previous study. Most H and D atoms were identified at essentially the same positions in both the neutron-only and the X-ray/neutron joint refinements. Nevertheless, neutron-only refinement was found to be less effective than joint refinement in providing very accurate heavy-atom coordinates that lead to significant improvement of the neutron scattering length density map, especially for the active-site cofactor. Consequently, it was confirmed that X-ray/neutron joint refinement is crucial for determination of the real chemical structure of the catalytic site of the enzyme.

Keywords: X-ray/neutron joint refinement; copper amine oxidases; neutron crystallography; quinone cofactor.

Grants and funding

This work was supported by JSPS KAKENHI Grant Nos. JP23770127, JP26440037 and 20H05448 to TM and JP16KT0055 and 19K05694 to TO from the Japan Society for the Promotion of Science and by funding from the Network Joint Research Center for Materials and Devices.