Molecular Playground/DnaK: Difference between revisions

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Joseph Tilitsky, Michal Harel

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 ===Drug Target===
-Since DnaK is critically positioned in the proteostasis system of many organsims it has been the target of choice for anti microbial and anti cancer therapy. Inhibitors of this enzyme are essentially folate mimics, methotrexate which was first designed to inhibit <scene name='User:Karan_Hingorani/sandbox_2/Humandhfr_nad_metho_1/1'>Human DHFR</scene> and used as therapy for cancer and autoimmune disorders. Another folate mimic Trimethoprim was developed as an anti bacterial agent, having much more binding specificity to bacterial DHFR than its mammalian counterpart. Both drugs bind in the active site of the enzyme and are irreversibly bound thus ablating enzyme activity.[http://www.ncbi.nlm.nih.gov/pubmed/3054871] [http://www.ncbi.nlm.nih.gov/pubmed/15681865?dopt=Abstract].
+Since DnaK is critically positioned in the proteostasis system of many organisms, including humans, it represents a tempting target for anti-cancer and neurodegenerative disease therapies. Recent efforts to develop a competitive inhibitor for DnaK, and Hsp70s in general, have met with only marginal success.[http://www.ncbi.nlm.nih.gov/pubmed/24312699] Recently, interactions between Hsp70s and its co-chaperones have been targeted for drug development, but with no leads currently in clinical trials.[http://www.ncbi.nlm.nih.gov/pubmed/22920901]
 ===3D structures of Hsp70===
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 . Zhuravleva A. et al. Cell 2012
+. Li X. et al. ACS Med Chem Lett 2013
+. Assimon VA. et al. Curr Pharm Des 2013