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Biocrystallization is the formation of crystals from organic macromolecules by living organisms. This may be a stress response, or a normal part of metabolism such as processes that dispose of waste compounds. Template mediated biocrystallization is qualitatively different from in vitro crystallization. Inhibitors of biocrystallization are of interest in drug design efforts against pathogens that feed on blood, since many of these organisms use this process to safely dispose of heme.
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DNA
Under severe stress conditions the bacteria Escherichia coli protects its DNA from damage by sequestering it within a crystalline structure.[1] This process is mediated by the stress response protein Dps and allows the bacteria to survive varied assaults such as oxidative stress, heat shock, ultraviolet light, gamma radiation and extremes of pH.[2][3]
Heme
Blood feeding organisms digest hemoglobin and release high quantities of free toxic heme. To avoid destruction by this molecule, the parasite biocrystallizes heme to form hemozoin.[5] To date, the only definitively characterized product of hematin disposal is the pigment hemozoin. Heme biocrystallization has been found in blood feeding organisms of great medical importance including Plasmodium, Rhodnius and Schistosoma. Heme biocrystallization is inhibited by quinoline antimalarials, the biocrystallization inhibitor Chloroquine is one of the best antimicrobials ever developed.
Targeting heme biocrystallization remains one of the most promising avenues for antimalarial drug development because the drug target is highly specific to the malarial parasite, and outside the genetic control of the parasite.
See also
References
- ^ Wolf SG, Frenkiel D, Arad T, Finkel SE, Kolter R, Minsky A (July 1999). "DNA protection by stress-induced biocrystallization". Nature 400 (6739): 83–5. doi:. PMID 10403254.
- ^ Nair S, Finkel SE (July 2004). "Dps protects cells against multiple stresses during stationary phase". J. Bacteriol. 186 (13): 4192–8. doi:. PMID 15205421.
- ^ Frenkiel-krispin, D.; Minsky, A. (2002). "Biocrystallization: A last-resort survival strategy in bacteria". ASM News 68 (6). Retrieved on 2008-05-05.
- ^ Hempelmann E, Marques HM. (September 1994). "Analysis of malaria pigment from Plasmodium falciparum". J Pharmacol Toxicol Methods 32 (1): 25-30. PMID 7833503.
- ^ Hempelmann E (March 2007). "Hemozoin biocrystallization in Plasmodium falciparum and the antimalarial activity of crystallization inhibitors". Parasitol. Res. 100 (4): 671–6. doi:. PMID 17111179.
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