title: Tyrosine aminotransferase from Leishmania infantum: A new drug target candidate.
abstract: 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.
authors.affiliation: Departamento de Microbiología Molecular y Servicio de Bioinformática y Bioestadística, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), calle Ramiro de Maeztu, 9, 28040 Madrid, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Moreno
authors.affiliation: Departamento de Microbiología Molecular y Servicio de Bioinformática y Bioestadística, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), calle Ramiro de Maeztu, 9, 28040 Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Departamento de Microbiología Molecular y Servicio de Bioinformática y Bioestadística, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), calle Ramiro de Maeztu, 9, 28040 Madrid, Spain.
authors.forename: Pedro Jose
authors.initials: PJ
authors.lastname: Alcolea
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA ; Seattle Biomedical Research Institute, 307 Westlake Avenue North, Seattle, WA 98109, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Abramov
authors.affiliation: Departamento de Microbiología Molecular y Servicio de Bioinformática y Bioestadística, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), calle Ramiro de Maeztu, 9, 28040 Madrid, Spain.
authors.forename: Mario García
authors.initials: MG
authors.lastname: de Lacoba
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA ; Emerald Bio Inc., 7869 NE Day Road West, Bainbridge Island, WA 98110, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Abendroth
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA ; Seattle Biomedical Research Institute, 307 Westlake Avenue North, Seattle, WA 98109, USA.
authors.forename: Sunny
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA ; Emerald Bio Inc., 7869 NE Day Road West, Bainbridge Island, WA 98110, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Edwards
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA ; Emerald Bio Inc., 7869 NE Day Road West, Bainbridge Island, WA 98110, USA.
authors.forename: Don
authors.initials: D
authors.lastname: Lorimer
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA ; Seattle Biomedical Research Institute, 307 Westlake Avenue North, Seattle, WA 98109, USA ; Department of Global Health, University of Washington, Seattle, WA 98125, USA ; Department of Biomedical Informatics & Medical Education, University of Washington, Seattle, WA 98125, USA.
authors.forename: Peter John
authors.initials: PJ
authors.lastname: Myler
authors.affiliation: Departamento de Microbiología Molecular y Servicio de Bioinformática y Bioestadística, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), calle Ramiro de Maeztu, 9, 28040 Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Larraga
keywords: Infectivity; KMTB; Leishmania infantum; Tyrosine aminotransferase