6QWG

Serial Femtosecond Crystallography Structure of Cu Nitrite Reductase from Achromobacter cycloclastes: Nitrite complex at Room Temperature

Summary for 6QWG

• Entry DOI: 10.2210/pdb6qwg/pdb
• Descriptor: Copper-containing nitrite reductase, NITRITE ION, COPPER (II) ION, ... (4 entities in total)
• Functional Keywords: copper nitrite reductase, serial femtosecond crystallography, ligand binding, damage free structure, oxidoreductase
• Biological source: Achromobacter cycloclastes
• Total number of polymer chains: 1
• Total formula weight: 36695.30

Authors

Ebrahim, A.E.,Moreno-Chicano, T.,Appleby, M.V.,Worrall, J.W.,Duyvesteyn, H.M.E.,Strange, R.W.,Beale, J.,Axford, D.,Sherrell, D.A.,Sugimoto, H.,Owada, S.,Tono, K.,Owen, R.L. (deposition date: 2019-03-05, release date: 2019-11-20, Last modification date: 2024-01-24)

Primary citation

Moreno-Chicano, T.,Ebrahim, A.,Axford, D.,Appleby, M.V.,Beale, J.H.,Chaplin, A.K.,Duyvesteyn, H.M.E.,Ghiladi, R.A.,Owada, S.,Sherrell, D.A.,Strange, R.W.,Sugimoto, H.,Tono, K.,Worrall, J.A.R.,Owen, R.L.,Hough, M.A.
High-throughput structures of protein-ligand complexes at room temperature using serial femtosecond crystallography.
Iucrj, 6:1074-1085, 2019

PubMed Abstract: High-throughput X-ray crystal structures of protein-ligand complexes are critical to pharmaceutical drug development. However, cryocooling of crystals and X-ray radiation damage may distort the observed ligand binding. Serial femtosecond crystallography (SFX) using X-ray free-electron lasers (XFELs) can produce radiation-damage-free room-temperature structures. Ligand-binding studies using SFX have received only modest attention, partly owing to limited beamtime availability and the large quantity of sample that is required per structure determination. Here, a high-throughput approach to determine room-temperature damage-free structures with excellent sample and time efficiency is demonstrated, allowing complexes to be characterized rapidly and without prohibitive sample requirements. This yields high-quality difference density maps allowing unambiguous ligand placement. Crucially, it is demonstrated that ligands similar in size or smaller than those used in fragment-based drug design may be clearly identified in data sets obtained from <1000 diffraction images. This efficiency in both sample and XFEL beamtime opens the door to true high-throughput screening of protein-ligand complexes using SFX.

PubMed: 31709063
DOI: 10.1107/S2052252519011655

Experimental method

X-RAY DIFFRACTION (1.9 Å)