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Title: Nanocrystallography measurements of early stage synthetic malaria pigment

Abstract

The recent availability of extremely intense, femtosecond X-ray free-electron laser (XFEL) sources has spurred the development of serial femtosecond nanocrystallography (SFX). Here, SFX is used to analyze nanoscale crystals of β-hematin, the synthetic form of hemozoin which is a waste by-product of the malaria parasite. This analysis reveals significant differences in β-hematin data collected during SFX and synchrotron crystallography experiments. To interpret these differences two possibilities are considered: structural differences between the nanocrystal and larger crystalline forms of β-hematin, and radiation damage. Simulation studies show that structural inhomogeneity appears at present to provide a better fit to the experimental data. If confirmed, these observations will have implications for designing compounds that inhibit hemozoin formation and suggest that, for some systems at least, additional information may be gained by comparing structures obtained from nanocrystals and macroscopic crystals of the same molecule.

Authors:
 [1];  [2]; ORCiD logo [3];  [1];  [1];  [4];  [4]; ORCiD logo [5]; ORCiD logo [6];  [7];  [1];  [8]; ORCiD logo [9];  [4]; ORCiD logo [9]
+ Show Author Affiliations
  1. Univ. of Melbourne (Australia). ARC Centre of Excellenece in Advanced Molecular Imaging
  2. Commonwealth Scientific and Industrial Research Organization (CSIRO), Parkville VIC (Australia)
  3. La Trobe Univ., Melbourne, VIC (Australia). ARC Centre of Excellence in Advanced Molecular Imaging, La Trobe Inst. of Medical Research; Walter and Eliza Hall Inst. of Medical Research, Parkville, VIC (Australia); Commonwealth Scientific and Industrial Research Organization (CSIRO) Manufacturing Flagship, Parkville VIC (Australia)
  4. Univ. of Melbourne (Australia). Dept. of Biochemistry and Molecular Biology, Molecular Science and Biotechnology Inst.
  5. SLAC National Accelerator Lab., Menlo Park, CA (United States). Linac Coherent Light Source
  6. BioXFEL STC Buffalo, NY (United States)
  7. Brookhaven National Lab. (BNL), Upton, NY (United States)
  8. Commonwealth Scientific and Industrial Research Organization (CSIRO), Parkville VIC (Australia); La Trobe Univ., Melbourne, VIC (Australia). ARC Centre of Excellence in Advanced Molecular Imaging, La Trobe Inst. of Medical Research
  9. La Trobe Univ., Melbourne, VIC (Australia). ARC Centre of Excellence in Advanced Molecular Imaging, La Trobe Inst. of Medical Research
Publication Date:
Research Org.:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States); Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1407496
Alternate Identifier(s):
OSTI ID: 1418317; OSTI ID: 1433955
Report Number(s):
BNL-203476-2018-JAAM
Journal ID: ISSN 1600-5767; JACGAR; PII: S1600576717012663; TRN: US1703051
Grant/Contract Number:  
AC02-76SF00515; SC0012704
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Applied Crystallography (Online)
Additional Journal Information:
Journal Name: Journal of Applied Crystallography (Online); Journal Volume: 50; Journal Issue: 5; Journal ID: ISSN 1600-5767
Publisher:
International Union of Crystallography
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; crystalloraphy; serial femtosecond nanocrystallography; malaria; crystalline disorder; structural inhomogeniety; 36 MATERIALS SCIENCE; crystallography

Citation Formats

Dilanian, Ruben A., Streltsov, Victor, Coughlan, Hannah D., Quiney, Harry M., Martin, Andrew V., Klonis, Nectarios, Dogovski, Con, Boutet, Sébastien, Messerschmidt, Marc, Williams, Garth J., Williams, Sophie, Phillips, Nicholas W., Nugent, Keith A., Tilley, Leann, and Abbey, Brian. Nanocrystallography measurements of early stage synthetic malaria pigment. United States: N. p., 2017. Web. doi:10.1107/s1600576717012663.
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Dilanian, Ruben A., Streltsov, Victor, Coughlan, Hannah D., Quiney, Harry M., Martin, Andrew V., Klonis, Nectarios, Dogovski, Con, Boutet, Sébastien, Messerschmidt, Marc, Williams, Garth J., Williams, Sophie, Phillips, Nicholas W., Nugent, Keith A., Tilley, Leann, & Abbey, Brian. Nanocrystallography measurements of early stage synthetic malaria pigment. United States. https://doi.org/10.1107/s1600576717012663
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Dilanian, Ruben A., Streltsov, Victor, Coughlan, Hannah D., Quiney, Harry M., Martin, Andrew V., Klonis, Nectarios, Dogovski, Con, Boutet, Sébastien, Messerschmidt, Marc, Williams, Garth J., Williams, Sophie, Phillips, Nicholas W., Nugent, Keith A., Tilley, Leann, and Abbey, Brian. Thu . "Nanocrystallography measurements of early stage synthetic malaria pigment". United States. https://doi.org/10.1107/s1600576717012663. https://www.osti.gov/servlets/purl/1407496.
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@article{osti_1407496,
title = {Nanocrystallography measurements of early stage synthetic malaria pigment},
author = {Dilanian, Ruben A. and Streltsov, Victor and Coughlan, Hannah D. and Quiney, Harry M. and Martin, Andrew V. and Klonis, Nectarios and Dogovski, Con and Boutet, Sébastien and Messerschmidt, Marc and Williams, Garth J. and Williams, Sophie and Phillips, Nicholas W. and Nugent, Keith A. and Tilley, Leann and Abbey, Brian},
abstractNote = {The recent availability of extremely intense, femtosecond X-ray free-electron laser (XFEL) sources has spurred the development of serial femtosecond nanocrystallography (SFX). Here, SFX is used to analyze nanoscale crystals of β-hematin, the synthetic form of hemozoin which is a waste by-product of the malaria parasite. This analysis reveals significant differences in β-hematin data collected during SFX and synchrotron crystallography experiments. To interpret these differences two possibilities are considered: structural differences between the nanocrystal and larger crystalline forms of β-hematin, and radiation damage. Simulation studies show that structural inhomogeneity appears at present to provide a better fit to the experimental data. If confirmed, these observations will have implications for designing compounds that inhibit hemozoin formation and suggest that, for some systems at least, additional information may be gained by comparing structures obtained from nanocrystals and macroscopic crystals of the same molecule.},
doi = {10.1107/s1600576717012663},
journal = {Journal of Applied Crystallography (Online)},
number = 5,
volume = 50,
place = {United States},
year = {Thu Sep 28 00:00:00 EDT 2017},
month = {Thu Sep 28 00:00:00 EDT 2017}
}
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Journal Article:
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Publisher's Version of Record
https://doi.org/10.1107/s1600576717012663
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Figures / Tables:

Figure 1 Figure 1: Synchrotron MX1 unfiltered crystal data (blue) and MX2 filtered crystal data (green) and SFX XRPD pattern (red) from β-hematin.
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    Works referencing / citing this record:

    TES X-ray Spectrometer at SLAC LCLS-II
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    • DOI: 10.3204/pubdb-2020-00138
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