skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Nanocrystallography measurements of early stage synthetic malaria pigment

Journal Article · · Journal of Applied Crystallography (Online)
 [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]
  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

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.

Research Organization:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States); Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-76SF00515; SC0012704
OSTI ID:
1407496
Alternate ID(s):
OSTI ID: 1418317; OSTI ID: 1433955
Report Number(s):
BNL-203476-2018-JAAM; JACGAR; PII: S1600576717012663; TRN: US1703051
Journal Information:
Journal of Applied Crystallography (Online), Vol. 50, Issue 5; ISSN 1600-5767
Publisher:
International Union of CrystallographyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 10 works
Citation information provided by
Web of Science

References (51)

X-ray laser–induced electron dynamics observed by femtosecond diffraction from nanocrystals of Buckminsterfullerene journal September 2016
Digestive-vacuole genesis and endocytic processes in the early intraerythrocytic stages of Plasmodium falciparum journal January 2010
Speciation of Ferriprotoporphyrin IX in Aqueous and Mixed Aqueous Solution Is Controlled by Solvent Identity, pH, and Salt Concentration journal August 2009
Heme, Heme Oxygenase, and Ferritin: How the Vascular Endothelium Survives (and Dies) in an Iron-Rich Environment journal December 2007
De novo protein crystal structure determination from X-ray free-electron laser data journal November 2013
Self-terminating diffraction gates femtosecond X-ray nanocrystallography measurements journal December 2011
Oxidative stress in malaria parasite-infected erythrocytes: host–parasite interactions journal February 2004
Haem polymerization in malaria journal November 1995
Characterization of the Products of the Heme Detoxification Pathway in Malarial Late Trophozoites by X-ray Diffraction journal January 1997
Powder pattern indexing with the dichotomy method journal September 2004
The Coherent X-ray Imaging (CXI) instrument at the Linac Coherent Light Source (LCLS) journal March 2010
Quinoline Binding Site on Malaria Pigment Crystal:  A Rational Pathway for Antimalaria Drug Design journal November 2002
Femtosecond X-ray protein nanocrystallography journal February 2011
Protein complex directs hemoglobin-to-hemozoin formation in Plasmodium falciparum journal March 2013
Insights into the Role of Heme in the Mechanism of Action of Antimalarials journal October 2012
Solution behavior of hematin under acidic conditions and implications for its interactions with chloroquine journal April 2010
Protein crystal screening and characterization for serial femtosecond nanocrystallography journal May 2016
Gas dynamic virtual nozzle for generation of microscopic droplet streams journal September 2008
Correction of intensities for preferred orientation in powder diffractometry: application of the March model journal August 1986
PowderX : Windows-95-based program for powder X-ray diffraction data processing journal August 1999
Correction of complex nonlinear signal response from a pixel array detector journal April 2015
Structure-Function Relationships in Chloroquine and Related 4-Aminoquinoline Antimalarials journal May 2001
Recent advances in understanding the mechanism of hemozoin (malaria pigment) formation journal May 2008
Alkoxide coordination of iron( iii ) protoporphyrin IX by antimalarial quinoline methanols: a key interaction observed in the solid-state and solution journal January 2015
FIT2D : a multi-purpose data reduction, analysis and visualization program journal March 2016
MFIT: Multiple spectra fitting program journal January 1989
Haemozoin: from melatonin pigment to drug target, diagnostic tool, and immune modulator journal October 2007
The CSPAD megapixel x-ray camera at LCLS conference October 2012
Cryo-protection of protein crystals against radiation damage in electron and X-ray diffraction journal July 1990
Synthetic Plasmodium-Like Hemozoin Activates the Immune Response: A Morphology - Function Study journal September 2009
Oriented nucleation of hemozoin at the digestive vacuole membrane in Plasmodium falciparum journal June 2012
Corrections to tabulated anomalous-scattering factors journal March 1990
Iron and heme metabolism in Plasmodium falciparum and the mechanism of action of artemisinins journal December 2013
Hematin−Hematin Self-Association States Involved in the Formation and Reactivity of the Malaria Parasite Pigment, Hemozoin journal August 2010
Free heme toxicity and its detoxification systems in human journal July 2005
Multiple spectroscopic and magnetic techniques show that chloroquine induces formation of the μ-oxo dimer of ferriprotoporphyrin IX journal April 2014
Solution structures of chloroquine–ferriheme complexes modeled using MD simulation and investigated by EXAFS spectroscopy journal January 2016
Indications of radiation damage in ferredoxin microcrystals using high-intensity X-FEL beams journal February 2015
Mechanisms of hematin crystallization and inhibition by the antimalarial drug chloroquine journal March 2015
The structure of malaria pigment β-haematin journal March 2000
The role of neutral lipid nanospheres in Plasmodium falciparum haem crystallization journal January 2007
Hemozoin: Oil versus water journal June 2008
Measurements of Long-range Electronic Correlations During Femtosecond Diffraction Experiments Performed on Nanocrystals of Buckminsterfullerene journal January 2017
Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites journal January 1992
Crystal Nucleation, Growth, and Morphology of the Synthetic Malaria Pigment β-Hematin and the Effect Thereon by Quinoline Additives:  The Malaria Pigment as a Target of Various Antimalarial Drugs journal March 2007
The Role of the Four Stereoisomers of the Heme Fe–O Cyclic Dimer in the Crystalline Phase Behavior of Synthetic Hemozoin: Relevance to Native Hemozoin Crystallization journal August 2011
The Malaria Pigment Hemozoin Comprises at Most Four Different Isomer Units in Two Crystalline Models: Chiral as Based on a Biochemical Hypothesis or Centrosymmetric Made of Enantiomorphous Sectors journal March 2014
Speciation and structure of ferriprotoporphyrin IX in aqueous solution: spectroscopic and diffusion measurements demonstrate dimerization, but not μ-oxo dimer formation journal September 2006
Injector for scattering measurements on fully solvated biospecies journal March 2012
Interplay Between Malaria, Crystalline Hemozoin Formation, and Antimalarial Drug Action and Design journal November 2008
RADDOSE-3D : time- and space-resolved modelling of dose in macromolecular crystallography journal June 2013

Cited By (5)

TES X-ray Spectrometer at SLAC LCLS-II journal September 2018
Electrical and magnetic properties of hemozoin nanocrystals journal November 2018
An outlook on using serial femtosecond crystallography in drug discovery journal May 2019
Protein phase separation and determinants of in cell crystallization journal November 2019
Protein phase separation and determinants of in cell crystallization text January 2019

Figures / Tables (4)