Biocrystallization

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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. 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.

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.[4] 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

  1. Wolf SG, Frenkiel D, Arad T, Finkel SE, Kolter R, Minsky A (1999). "DNA protection by stress-induced biocrystallization". Nature. 400 (6739): 83–5. doi:10.1038/21918. PMID 10403254. Unknown parameter |month= ignored (help)
  2. Nair S, Finkel SE (2004). "Dps protects cells against multiple stresses during stationary phase". J. Bacteriol. 186 (13): 4192–8. doi:10.1128/JB.186.13.4192-4198.2004. PMID 15205421. Unknown parameter |month= ignored (help)
  3. Frenkiel-krispin, D. (2002). "Biocrystallization: A last-resort survival strategy in bacteria". ASM News. 68 (6). Retrieved 2008-05-05. Unknown parameter |coauthors= ignored (help)
  4. Hempelmann E (2007). "Hemozoin biocrystallization in Plasmodium falciparum and the antimalarial activity of crystallization inhibitors". Parasitol. Res. 100 (4): 671–6. doi:10.1007/s00436-006-0313-x. PMID 17111179. Unknown parameter |month= ignored (help)

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