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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2014
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.
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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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