Open AccessCrystallization and preliminary X‐ray studies of the N‐domain of the Wilson disease associated protein
Author(s) -
Liu Lili,
O'Grady Christopher,
Dalrymple Sean A.,
Prasad Lata,
Dmitriev Oleg Y.,
Delbaere Louis T. J.
Publication year - 2009
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309109017023
Subject(s) - crystallography , crystallization , diffraction , domain (mathematical analysis) , x ray crystallography , synchrotron , crystal structure , x ray , crystal (programming language) , chemistry , physics , optics , mathematical analysis , programming language , mathematics , organic chemistry , computer science
Wilson disease associated protein (ATP7B) is essential for copper transport in human cells. Mutations that affect ATP7B function result in Wilson's disease, a chronic copper toxicosis. Disease‐causing mutations within the N‐domain of ATP7B (WND) are known to disrupt ATP binding, but a high‐resolution X‐ray structure of the ATP‐binding site has not been reported. The N‐domain was modified to delete the disordered loop comprising residues His1115–Asp1138 (WNDΔ 1115–1138 ). Unlike the wild‐type N‐domain, WNDΔ 1115–1138 formed good‐quality crystals. Synchrotron diffraction data have been collected from WNDΔ 1115–1138 at the Canadian Light Source. A native WNDΔ 1115–1138 crystal diffracted to 1.7 Å resolution and belonged to space group P 4 2 2 1 2, with unit‐cell parameters a = 39.2, b = 39.2, c = 168.9 Å. MAD data were collected to 2.7 Å resolution from a SeMet‐derivative crystal with unit‐cell parameters a = 38.4, b = 38.4, c = 166.7 Å. The WNDΔ 1115–1138 structure is likely to be solved by phasing from multiwavelength anomalous diffraction (MAD) experiments.