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Title: Mix-and-diffuse serial synchrotron crystallography

Unravelling the interaction of biological macromolecules with ligands and substrates at high spatial and temporal resolution remains a major challenge in structural biology. The development of serial crystallography methods at X-ray free-electron lasers and subsequently at synchrotron light sources allows new approaches to tackle this challenge. Here, a new polyimide tape drive designed for mix-and-diffuse serial crystallography experiments is reported. The structure of lysozyme bound by the competitive inhibitor chitotriose was determined using this device in combination with microfluidic mixers. The electron densities obtained from mixing times of 2 and 50 s show clear binding of chitotriose to the enzyme at a high level of detail. Here, the success of this approach shows the potential for high-throughput drug screening and even structural enzymology on short timescales at bright synchrotron light sources.
Authors:
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  1. Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)
  2. California State Univ., Northridge, CA (United States)
  3. Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Univ. of Hamburg, Hamburg (Germany)
  4. Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Norwegian Univ. of Science and Technology, Trondheim (Norway)
  5. Uppsala Univ., Uppsala (Sweden)
  6. Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); European X-ray Free-Electron Laser Facility GmbH (XFEL), Schenefeld (Germany)
  7. Univ. of Oxford, Oxford (England)
  8. SLAC National Accelerator Lab., Menlo Park, CA (United States)
  9. Fachhochschule Lubeck, Lubeck (Germany)
Publication Date:
Grant/Contract Number:
AC02-76SF00515; FP7/2007-2013; ERC-614507-Küpper; DFG-EXC1074
Type:
Accepted Manuscript
Journal Name:
IUCrJ
Additional Journal Information:
Journal Volume: 4; Journal Issue: 6; Journal ID: ISSN 2052-2525
Publisher:
International Union of Crystallography
Research Org:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; drug discovery; protein structure; X-ray crystallography; serial crystallography; time-resolved studies; lysozyme
OSTI Identifier:
1410554