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Proximal ADP-ribose Hydrolysis in Trypanosomatids is Catalyzed by a Macrodomain
ADP-ribosylation is a ubiquitous protein modification utilized by both prokaryotes and eukaryotes for several cellular functions, such as DNA repair, proliferation, and cell signaling. Higher eukaryotes, such as humans, utilize various enzymes to reverse the modification and to regulate ADP-ribose d...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827093/ https://www.ncbi.nlm.nih.gov/pubmed/27064071 http://dx.doi.org/10.1038/srep24213 |
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author | Haikarainen, Teemu Lehtiö, Lari |
author_facet | Haikarainen, Teemu Lehtiö, Lari |
author_sort | Haikarainen, Teemu |
collection | PubMed |
description | ADP-ribosylation is a ubiquitous protein modification utilized by both prokaryotes and eukaryotes for several cellular functions, such as DNA repair, proliferation, and cell signaling. Higher eukaryotes, such as humans, utilize various enzymes to reverse the modification and to regulate ADP-ribose dependent signaling. In contrast, some lower eukaryotes, including trypanosomatids, lack many of these enzymes and therefore have a much more simplified ADP-ribose metabolism. Here we identified and characterized ADP-ribose hydrolases from Trypanosoma brucei and Trypanosoma cruzi, which are homologous to human O-acetyl-ADP-ribose deacetylases MacroD1 and MacroD2. The enzymes are capable for hydrolysis of protein linked ADP-ribose and a product of sirtuin-mediated lysine deacetylation, O-acetyl-ADP-ribose. Crystal structures of the trypanosomatid macrodomains revealed a conserved catalytic site with distinct differences to human MacroD1 and MacroD2. |
format | Online Article Text |
id | pubmed-4827093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48270932016-04-19 Proximal ADP-ribose Hydrolysis in Trypanosomatids is Catalyzed by a Macrodomain Haikarainen, Teemu Lehtiö, Lari Sci Rep Article ADP-ribosylation is a ubiquitous protein modification utilized by both prokaryotes and eukaryotes for several cellular functions, such as DNA repair, proliferation, and cell signaling. Higher eukaryotes, such as humans, utilize various enzymes to reverse the modification and to regulate ADP-ribose dependent signaling. In contrast, some lower eukaryotes, including trypanosomatids, lack many of these enzymes and therefore have a much more simplified ADP-ribose metabolism. Here we identified and characterized ADP-ribose hydrolases from Trypanosoma brucei and Trypanosoma cruzi, which are homologous to human O-acetyl-ADP-ribose deacetylases MacroD1 and MacroD2. The enzymes are capable for hydrolysis of protein linked ADP-ribose and a product of sirtuin-mediated lysine deacetylation, O-acetyl-ADP-ribose. Crystal structures of the trypanosomatid macrodomains revealed a conserved catalytic site with distinct differences to human MacroD1 and MacroD2. Nature Publishing Group 2016-04-11 /pmc/articles/PMC4827093/ /pubmed/27064071 http://dx.doi.org/10.1038/srep24213 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Haikarainen, Teemu Lehtiö, Lari Proximal ADP-ribose Hydrolysis in Trypanosomatids is Catalyzed by a Macrodomain |
title | Proximal ADP-ribose Hydrolysis in Trypanosomatids is Catalyzed by a Macrodomain |
title_full | Proximal ADP-ribose Hydrolysis in Trypanosomatids is Catalyzed by a Macrodomain |
title_fullStr | Proximal ADP-ribose Hydrolysis in Trypanosomatids is Catalyzed by a Macrodomain |
title_full_unstemmed | Proximal ADP-ribose Hydrolysis in Trypanosomatids is Catalyzed by a Macrodomain |
title_short | Proximal ADP-ribose Hydrolysis in Trypanosomatids is Catalyzed by a Macrodomain |
title_sort | proximal adp-ribose hydrolysis in trypanosomatids is catalyzed by a macrodomain |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827093/ https://www.ncbi.nlm.nih.gov/pubmed/27064071 http://dx.doi.org/10.1038/srep24213 |
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