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J Mol Graph Model. 2015 Nov;62:342-361. doi: 10.1016/j.jmgm.2015.10.006. Epub 2015 Oct 19.

Homology modeling of parasite histone deacetylases to guide the structure-based design of selective inhibitors.

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Institute of Pharmacy, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Germany.
Univ Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000 Lille, France.
Département de Biologie Structurale Intégrative, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UDS), CNRS, INSERM, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France.
Institute of Pharmacy, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Germany. Electronic address:


Histone deacetylases (HDACs) are promising epigenetic targets for the treatment of various diseases, including cancer and neurodegenerative disorders. There is evidence that they can also be addressed to treat parasitic infections. Recently, the first X-ray structure of a parasite HDAC was published, Schistosoma mansoni HDAC8, giving structural insights into its inhibition. However, most of the targets from parasites of interest still lack this structural information. Therefore, we prepared homology models of relevant parasitic HDACs and compared them to human and S. mansoni HDACs. The information about known S. mansoni HDAC8 inhibitors and compounds that affect the growth of Trypanosoma, Leishmania and Plasmodium species was used to validate the models by docking and molecular dynamics studies. Our results provide analysis of structural features of parasitic HDACs and should be helpful for selecting promising candidates for biological testing and for structure-based optimisation of parasite-specific inhibitors.


Epigenetics; Histone deacetylases; Homology modeling; Molecular docking; Molecular modeling; Parasitic diseases

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