Experimental phasing opportunities for macromolecular crystallography at very long wavelengths

• Published in: Communications chemistry Vol. 6; no. 1; pp. 219 - 11
• Main Authors: El Omari, Kamel, Duman, Ramona, Mykhaylyk, Vitaliy, Orr, Christian M., Latimer-Smith, Merlyn, Winter, Graeme, Grama, Vinay, Qu, Feng, Bountra, Kiran, Kwong, Hok Sau, Romano, Maria, Reis, Rosana I., Vogeley, Lutz, Vecchia, Luca, Owen, C. David, Wittmann, Sina, Renner, Max, Senda, Miki, Matsugaki, Naohiro, Kawano, Yoshiaki, Bowden, Thomas A., Moraes, Isabel, Grimes, Jonathan M., Mancini, Erika J., Walsh, Martin A., Guzzo, Cristiane R., Owens, Raymond J., Jones, E. Yvonne, Brown, David G., Stuart, Dave I., Beis, Konstantinos, Wagner, Armin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12-10-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/45/535/1266; 631/535/1266; 639/638/11/879; 639/638/45/535/1266; Artificial intelligence; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Chlorine; Crystallography; Diamonds; Light sources; Molecular structure; Particle beams; Synchrotrons; Wavelengths
• ISSN: 2399-3669; 2399-3669
• DOI: 10.1038/s42004-023-01014-0

Despite recent advances in cryo-electron microscopy and artificial intelligence-based model predictions, a significant fraction of structure determinations by macromolecular crystallography still requires experimental phasing, usually by means of single-wavelength anomalous diffraction (SAD) techniques. Most synchrotron beamlines provide highly brilliant beams of X-rays of between 0.7 and 2 Å wavelength. Use of longer wavelengths to access the absorption edges of biologically important lighter atoms such as calcium, potassium, chlorine, sulfur and phosphorus for native-SAD phasing is attractive but technically highly challenging. The long-wavelength beamline I23 at Diamond Light Source overcomes these limitations and extends the accessible wavelength range to
λ
 = 5.9 Å. Here we report 22 macromolecular structures solved in this extended wavelength range, using anomalous scattering from a range of elements which demonstrate the routine feasibility of lighter atom phasing. We suggest that, in light of its advantages, long-wavelength crystallography is a compelling option for experimental phasing.
Structural biology has undergone a revolution thanks to cryo-EM and artificial intelligence-based model predictions; nonetheless, experimental phasing continues to be essential. Here, the authors utilize the long-wavelength I23 beamline at Diamond Light Source to solve macromolecular structures using single-wavelength anomalous diffraction techniques, showcasing their proficiency in phasing with lighter atoms.