| Author | Marek, Martin | |
| Author | Ramos-Morales, Elizabeth | |
| Author | Picchi-Constante, Gisele Fernanda Assine | |
| Author | Bayer, Theresa | |
| Author | Norström, Carina | |
| Author | Herp, Daniel | |
| Author | Sales-Junior, Policarpo A. | |
| Author | Guerra-Slompo, Eloise Pavão | |
| Author | Hausmann, Kristin | |
| Author | Chakrabarti, Alokta | |
| Author | Shaik, Tajith B. | |
| Author | Merz, Annika | |
| Author | Troesch, Edouard | |
| Author | Schmidtkunz, Karin | |
| Author | Goldenberg, Samuel | |
| Author | Pierce, Raymond J. | |
| Author | Mourão, Marina M. | |
| Author | Jung, Manfred | |
| Author | Schultz, Johan | |
| Author | Sippl, Wolfgang | |
| Author | Zanchin, Nilson Ivo Tonin | |
| Author | Romier, Christophe | |
| Access date | 2022-01-14T19:48:38Z | |
| Available date | 2022-01-14T19:48:38Z | |
| Document date | 2021 | |
| Citation | MAREK, Martin et al. Species-selective targeting of pathogens revealed by the atypical structure and active site of Trypanosoma cruzi histone deacetylase DAC2. Cell Reports v. 37, n. 110129, p. 1–27, 2021. | pt_BR |
| ISSN | 2211-1247 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/50761 | |
| Language | por | pt_BR |
| Publisher | Cell Press | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | HDACs | pt_BR |
| Subject in Portuguese | Antiparasitários | pt_BR |
| Title | Species-selective targeting of pathogens revealed by the atypical structure and active site of Trypanosoma cruzi histone deacetylase DAC2 | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1016/j.celrep.2021.110129 | |
| Abstract | Writing and erasing of posttranslational modifications are crucial to phenotypic plasticity and antigenic variation of eukaryotic pathogens. Targeting pathogens’ modification machineries, thus, represents a valid approach to fighting parasitic diseases. However, identification of parasitic targets and the development of selective anti-parasitic drugs still represent major bottlenecks. Here, we show that the zinc-dependent histone deacetylases (HDACs) of the protozoan parasite Trypanosoma cruzi are key regulators that have significantly diverged from their human counterparts. Depletion of T. cruzi class I HDACs tcDAC1 and tcDAC2 compromises cell-cycle progression and division, leading to cell death. Notably, tcDAC2 displays a deacetylase activity essential to the parasite and shows major structural differences with human HDACs. Specifically, tcDAC2 harbors a modular active site with a unique subpocket targeted by inhibitors showing substantial anti-parasitic effects in cellulo and in vivo. Thus, the targeting of the many atypical HDACs in pathogens can enable anti-parasitic selective chemical impairment. | pt_BR |
| Affilliation | Université de Strasbourg, CNRS, INSERM. Institut de Génétique et de Biologie Moléculaire et Cellulaire. Illkirch, France. / Université de Strasbourg, CNRS, INSERM. Institut de Génétique et de Biologie Moléculaire et Cellulaire. Department of Integrated Structural Biology. Illkirch, France. | pt_BR |
| Affilliation | Université de Strasbourg, CNRS, INSERM. Institut de Génétique et de Biologie Moléculaire et Cellulaire. Illkirch, France. / Université de Strasbourg, CNRS, INSERM. Institut de Génétique et de Biologie Moléculaire et Cellulaire. Department of Integrated Structural Biology. Illkirch, France. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
| Affilliation | Institute of Pharmacy. Martin-Luther-Universität Halle-Wittenberg. Halle (Saale), Germany. | pt_BR |
| Affilliation | Kancera AB. Karolinska Institutet Science Park. Solna, Sweden. | pt_BR |
| Affilliation | Institute of Pharmaceutical Sciences. Albert-Ludwigs-Universität Freiburg. Freiburg, Germany. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
| Affilliation | Institute of Pharmacy. Martin-Luther-Universität Halle-Wittenberg. Halle (Saale), Germany. | pt_BR |
| Affilliation | Institute of Pharmaceutical Sciences. Albert-Ludwigs-Universität Freiburg. Freiburg, Germany. | pt_BR |
| Affilliation | Université de Strasbourg, CNRS, INSERM. Institut de Génétique et de Biologie Moléculaire et Cellulaire. Illkirch, France. / Université de Strasbourg, CNRS, INSERM. Institut de Génétique et de Biologie Moléculaire et Cellulaire. Department of Integrated Structural Biology. Illkirch, France. | pt_BR |
| Affilliation | Institute of Pharmaceutical Sciences. Albert-Ludwigs-Universität Freiburg. Freiburg, Germany. | pt_BR |
| Affilliation | Université de Strasbourg, CNRS, INSERM. Institut de Génétique et de Biologie Moléculaire et Cellulaire. Illkirch, France. / Université de Strasbourg, CNRS, INSERM. Institut de Génétique et de Biologie Moléculaire et Cellulaire. Department of Integrated Structural Biology. Illkirch, France. | pt_BR |
| Affilliation | Institute of Pharmaceutical Sciences. Albert-Ludwigs-Universität Freiburg. Freiburg, Germany. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
| Affilliation | Université de Lille, CNRS, INSERM, CHU Lille. Lille, France. / Institut Pasteur de Lille. Lille, France. / CIIL - Centre d’Infection et d’Immunité de Lille. Lille, France. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Institute of Pharmaceutical Sciences. Albert-Ludwigs-Universität Freiburg. Freiburg, Germany. | pt_BR |
| Affilliation | Kancera AB. Karolinska Institutet Science Park. Solna, Sweden. | pt_BR |
| Affilliation | Institute of Pharmacy. Martin-Luther-Universität Halle-Wittenberg. Halle (Saale), Germany. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
| Affilliation | Université de Strasbourg, CNRS, INSERM. Institut de Génétique et de Biologie Moléculaire et Cellulaire. Illkirch, France. / Université de Strasbourg, CNRS, INSERM. Institut de Génétique et de Biologie Moléculaire et Cellulaire. Department of Integrated Structural Biology. Illkirch, France. | pt_BR |
| Subject | zinc-dependent Histone Deacetylases | pt_BR |
| Subject | Anti-parasitic | pt_BR |
| Subject | Cell Death | pt_BR |
| Subject in Spanish | Histona Desacetilasas | pt_BR |
| Subject in Spanish | Muerte Celular | pt_BR |
| Subject in French | Histone deacetylases | pt_BR |
| Subject in French | Mort cellulaire | pt_BR |
| DeCS | Histona Desacetilases | pt_BR |
| DeCS | Trypanosoma cruzi | pt_BR |
| DeCS | Morte Celular | pt_BR |
