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Tyrosine aminotransferase from Leishmania infantum: A new drug target candidate
Leishmania infantum is the etiological agent of zoonotic visceral leishmaniasis in the Mediterranean basin. The disease is fatal without treatment, which has been based on antimonial pentavalents for more than 60 years. Due to resistances, relapses and toxicity to current treatment, the development...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266777/ https://www.ncbi.nlm.nih.gov/pubmed/25516846 http://dx.doi.org/10.1016/j.ijpddr.2014.06.001 |
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author | Moreno, Miguel Angel Alonso, Ana Alcolea, Pedro Jose Abramov, Ariel de Lacoba, Mario García Abendroth, Jan Zhang, Sunny Edwards, Thomas Lorimer, Don Myler, Peter John Larraga, Vicente |
author_facet | Moreno, Miguel Angel Alonso, Ana Alcolea, Pedro Jose Abramov, Ariel de Lacoba, Mario García Abendroth, Jan Zhang, Sunny Edwards, Thomas Lorimer, Don Myler, Peter John Larraga, Vicente |
author_sort | Moreno, Miguel Angel |
collection | PubMed |
description | Leishmania infantum is the etiological agent of zoonotic visceral leishmaniasis in the Mediterranean basin. The disease is fatal without treatment, which has been based on antimonial pentavalents for more than 60 years. Due to resistances, relapses and toxicity to current treatment, the development of new drugs is required. The structure of the L. infantum tyrosine aminotransferase (LiTAT) has been recently solved showing important differences with the mammalian orthologue. The characterization of LiTAT is reported herein. This enzyme is cytoplasmic and is over-expressed in the more infective stages and nitric oxide resistant parasites. Unlike the mammalian TAT, LiTAT is able to use ketomethiobutyrate as co-substrate. The pharmacophore model of LiTAT with this specific co-substrate is described herein. This may allow the identification of new inhibitors present in the databases. All the data obtained support that LiTAT is a good target candidate for the development of new anti-leishmanial drugs. |
format | Online Article Text |
id | pubmed-4266777 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-42667772014-12-16 Tyrosine aminotransferase from Leishmania infantum: A new drug target candidate Moreno, Miguel Angel Alonso, Ana Alcolea, Pedro Jose Abramov, Ariel de Lacoba, Mario García Abendroth, Jan Zhang, Sunny Edwards, Thomas Lorimer, Don Myler, Peter John Larraga, Vicente Int J Parasitol Drugs Drug Resist Article Leishmania infantum is the etiological agent of zoonotic visceral leishmaniasis in the Mediterranean basin. The disease is fatal without treatment, which has been based on antimonial pentavalents for more than 60 years. Due to resistances, relapses and toxicity to current treatment, the development of new drugs is required. The structure of the L. infantum tyrosine aminotransferase (LiTAT) has been recently solved showing important differences with the mammalian orthologue. The characterization of LiTAT is reported herein. This enzyme is cytoplasmic and is over-expressed in the more infective stages and nitric oxide resistant parasites. Unlike the mammalian TAT, LiTAT is able to use ketomethiobutyrate as co-substrate. The pharmacophore model of LiTAT with this specific co-substrate is described herein. This may allow the identification of new inhibitors present in the databases. All the data obtained support that LiTAT is a good target candidate for the development of new anti-leishmanial drugs. Elsevier 2014-07-30 /pmc/articles/PMC4266777/ /pubmed/25516846 http://dx.doi.org/10.1016/j.ijpddr.2014.06.001 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Moreno, Miguel Angel Alonso, Ana Alcolea, Pedro Jose Abramov, Ariel de Lacoba, Mario García Abendroth, Jan Zhang, Sunny Edwards, Thomas Lorimer, Don Myler, Peter John Larraga, Vicente Tyrosine aminotransferase from Leishmania infantum: A new drug target candidate |
title | Tyrosine aminotransferase from Leishmania infantum: A new drug target candidate |
title_full | Tyrosine aminotransferase from Leishmania infantum: A new drug target candidate |
title_fullStr | Tyrosine aminotransferase from Leishmania infantum: A new drug target candidate |
title_full_unstemmed | Tyrosine aminotransferase from Leishmania infantum: A new drug target candidate |
title_short | Tyrosine aminotransferase from Leishmania infantum: A new drug target candidate |
title_sort | tyrosine aminotransferase from leishmania infantum: a new drug target candidate |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266777/ https://www.ncbi.nlm.nih.gov/pubmed/25516846 http://dx.doi.org/10.1016/j.ijpddr.2014.06.001 |
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