Synchrotron radiation as a tool for macromolecular X-Ray Crystallography: A XXI century perspective

Marek Grabowski, David R. Cooper, Dariusz Brzezinski, Joanna M. Macnar, Ivan G. Shabalin, Marcin Cymborowski, Zbyszek Otwinowski, Wladek Minor

Research output: Contribution to journalArticlepeer-review

Abstract

Intense X-rays available at powerful synchrotron beamlines provide macromolecular crystallographers with an incomparable tool for investigating biological phenomena on an atomic scale. The resulting insights into the mechanism's underlying biological processes have played an essential role and shaped biomedical sciences during the last 30 years, considered the “golden age” of structural biology. In this review, we analyze selected aspects of the impact of synchrotron radiation on structural biology. Synchrotron beamlines have been used to determine over 70% of all macromolecular structures deposited into the Protein Data Bank (PDB). These structures were deposited by over 13,000 different research groups. Interestingly, despite the impressive advances in synchrotron technologies, the median resolution of macromolecular structures determined using synchrotrons has remained constant throughout the last 30 years, at about 2 Å. Similarly, the median times from the data collection to the deposition and release have not changed significantly. We describe challenges to reproducibility related to recording all relevant data and metadata during the synchrotron experiments, including diffraction images. Finally, we discuss some of the recent opinions suggesting a diminishing importance of X-ray crystallography due to impressive advances in Cryo-EM and theoretical modeling. We believe that synchrotrons of the future will increasingly evolve towards a life science center model, where X-ray crystallography, Cryo-EM, other experimental and computational resources, and knowledge are encompassed within a versatile research facility. The recent response of crystallographers to the COVID-19 pandemic suggests that X-ray crystallography conducted at synchrotron beamlines will continue to play an essential role in structural biology and drug discovery for years to come.

Original languageEnglish (US)
Pages (from-to)30-40
Number of pages11
JournalNuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms
Volume489
DOIs
StatePublished - Feb 15 2021

Keywords

  • COVID-19
  • Data management
  • Databases
  • Drug discovery
  • Macromolecular crystallography
  • Structural biology
  • Synchrotron radiation

ASJC Scopus subject areas

  • Nuclear and High Energy Physics
  • Instrumentation

Fingerprint

Dive into the research topics of 'Synchrotron radiation as a tool for macromolecular X-Ray Crystallography: A XXI century perspective'. Together they form a unique fingerprint.

Cite this