Structural basis for the relaxed substrate selectivity of Leishmania mexicana broad specificity aminotransferase

Autores
Wen, Jiang; Nowicki, Cristina; Blankenfeldt, Wulf
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Leishmania species are early branching eukaryotic parasites that cause difficult-to-treat tissue-damaging diseases known as leishmaniases. As a hallmark of their parasitic lifestyle, Leishmaniae express a number of aminotransferases that are involved in important cellular processes and exhibit broader substrate specificity than their mammalian host's counterparts. Here, we have determined the crystal structure of the broad specificity aminotransferase from Leishmania mexicana (LmexBSAT) at 1.91 Å resolution. LmexBSAT is a homodimer and belongs to the α-branch of family-I aminotransferases. Despite the fact that the protein was crystallized in the absence of substrates and has lost the pyridoxal-5′-phosphate (PLP) cofactor during crystallization, the structure resembles the closed, ligand-bound form of related enzymes such as chicken cytosolic aspartate aminotransferase. Its broader substrate specificity seems to be rooted in increased flexibility of a substrate-binding arginine (R291) and the interactions of this residue with the N-terminus of the second chain of the dimer.
Fil: Wen, Jiang. Universitat Dortmund; Alemania. Institut Max Planck fur Molekulare Physiologie; Alemania
Fil: Nowicki, Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Blankenfeldt, Wulf. Institut Max Planck fur Molekulare Physiologie; Alemania
Materia
AMINOTRANSFERASE
DRUG DESIGN
LEISHMANIASIS
METABOLISM
SUBSTRATE SPECIFICITY
TRANSAMINATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/94396
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/94396
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Structural basis for the relaxed substrate selectivity of Leishmania mexicana broad specificity aminotransferaseWen, JiangNowicki, CristinaBlankenfeldt, WulfAMINOTRANSFERASEDRUG DESIGNLEISHMANIASISMETABOLISMSUBSTRATE SPECIFICITYTRANSAMINATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Leishmania species are early branching eukaryotic parasites that cause difficult-to-treat tissue-damaging diseases known as leishmaniases. As a hallmark of their parasitic lifestyle, Leishmaniae express a number of aminotransferases that are involved in important cellular processes and exhibit broader substrate specificity than their mammalian host's counterparts. Here, we have determined the crystal structure of the broad specificity aminotransferase from Leishmania mexicana (LmexBSAT) at 1.91 Å resolution. LmexBSAT is a homodimer and belongs to the α-branch of family-I aminotransferases. Despite the fact that the protein was crystallized in the absence of substrates and has lost the pyridoxal-5′-phosphate (PLP) cofactor during crystallization, the structure resembles the closed, ligand-bound form of related enzymes such as chicken cytosolic aspartate aminotransferase. Its broader substrate specificity seems to be rooted in increased flexibility of a substrate-binding arginine (R291) and the interactions of this residue with the N-terminus of the second chain of the dimer.Fil: Wen, Jiang. Universitat Dortmund; Alemania. Institut Max Planck fur Molekulare Physiologie; AlemaniaFil: Nowicki, Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Blankenfeldt, Wulf. Institut Max Planck fur Molekulare Physiologie; AlemaniaElsevier Science2015-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/94396Wen, Jiang; Nowicki, Cristina; Blankenfeldt, Wulf; Structural basis for the relaxed substrate selectivity of Leishmania mexicana broad specificity aminotransferase; Elsevier Science; Molecular and Biochemical Parasitology; 202; 2; 8-2015; 34-370166-6851CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0166685115300311info:eu-repo/semantics/altIdentifier/doi/10.1016/j.molbiopara.2015.09.007info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:34:23Zoai:ri.conicet.gov.ar:11336/94396instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:34:23.927CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Structural basis for the relaxed substrate selectivity of Leishmania mexicana broad specificity aminotransferase
title Structural basis for the relaxed substrate selectivity of Leishmania mexicana broad specificity aminotransferase
spellingShingle Structural basis for the relaxed substrate selectivity of Leishmania mexicana broad specificity aminotransferase
Wen, Jiang
AMINOTRANSFERASE
DRUG DESIGN
LEISHMANIASIS
METABOLISM
SUBSTRATE SPECIFICITY
TRANSAMINATION
title_short Structural basis for the relaxed substrate selectivity of Leishmania mexicana broad specificity aminotransferase
title_full Structural basis for the relaxed substrate selectivity of Leishmania mexicana broad specificity aminotransferase
title_fullStr Structural basis for the relaxed substrate selectivity of Leishmania mexicana broad specificity aminotransferase
title_full_unstemmed Structural basis for the relaxed substrate selectivity of Leishmania mexicana broad specificity aminotransferase
title_sort Structural basis for the relaxed substrate selectivity of Leishmania mexicana broad specificity aminotransferase
dc.creator.none.fl_str_mv Wen, Jiang
Nowicki, Cristina
Blankenfeldt, Wulf
author Wen, Jiang
author_facet Wen, Jiang
Nowicki, Cristina
Blankenfeldt, Wulf
author_role author
author2 Nowicki, Cristina
Blankenfeldt, Wulf
author2_role author
author
dc.subject.none.fl_str_mv AMINOTRANSFERASE
DRUG DESIGN
LEISHMANIASIS
METABOLISM
SUBSTRATE SPECIFICITY
TRANSAMINATION
topic AMINOTRANSFERASE
DRUG DESIGN
LEISHMANIASIS
METABOLISM
SUBSTRATE SPECIFICITY
TRANSAMINATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Leishmania species are early branching eukaryotic parasites that cause difficult-to-treat tissue-damaging diseases known as leishmaniases. As a hallmark of their parasitic lifestyle, Leishmaniae express a number of aminotransferases that are involved in important cellular processes and exhibit broader substrate specificity than their mammalian host's counterparts. Here, we have determined the crystal structure of the broad specificity aminotransferase from Leishmania mexicana (LmexBSAT) at 1.91 Å resolution. LmexBSAT is a homodimer and belongs to the α-branch of family-I aminotransferases. Despite the fact that the protein was crystallized in the absence of substrates and has lost the pyridoxal-5′-phosphate (PLP) cofactor during crystallization, the structure resembles the closed, ligand-bound form of related enzymes such as chicken cytosolic aspartate aminotransferase. Its broader substrate specificity seems to be rooted in increased flexibility of a substrate-binding arginine (R291) and the interactions of this residue with the N-terminus of the second chain of the dimer.
Fil: Wen, Jiang. Universitat Dortmund; Alemania. Institut Max Planck fur Molekulare Physiologie; Alemania
Fil: Nowicki, Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Blankenfeldt, Wulf. Institut Max Planck fur Molekulare Physiologie; Alemania
description Leishmania species are early branching eukaryotic parasites that cause difficult-to-treat tissue-damaging diseases known as leishmaniases. As a hallmark of their parasitic lifestyle, Leishmaniae express a number of aminotransferases that are involved in important cellular processes and exhibit broader substrate specificity than their mammalian host's counterparts. Here, we have determined the crystal structure of the broad specificity aminotransferase from Leishmania mexicana (LmexBSAT) at 1.91 Å resolution. LmexBSAT is a homodimer and belongs to the α-branch of family-I aminotransferases. Despite the fact that the protein was crystallized in the absence of substrates and has lost the pyridoxal-5′-phosphate (PLP) cofactor during crystallization, the structure resembles the closed, ligand-bound form of related enzymes such as chicken cytosolic aspartate aminotransferase. Its broader substrate specificity seems to be rooted in increased flexibility of a substrate-binding arginine (R291) and the interactions of this residue with the N-terminus of the second chain of the dimer.
publishDate 2015
dc.date.none.fl_str_mv 2015-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/94396
Wen, Jiang; Nowicki, Cristina; Blankenfeldt, Wulf; Structural basis for the relaxed substrate selectivity of Leishmania mexicana broad specificity aminotransferase; Elsevier Science; Molecular and Biochemical Parasitology; 202; 2; 8-2015; 34-37
0166-6851
CONICET Digital
CONICET
url http://hdl.handle.net/11336/94396
identifier_str_mv Wen, Jiang; Nowicki, Cristina; Blankenfeldt, Wulf; Structural basis for the relaxed substrate selectivity of Leishmania mexicana broad specificity aminotransferase; Elsevier Science; Molecular and Biochemical Parasitology; 202; 2; 8-2015; 34-37
0166-6851
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0166685115300311
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.molbiopara.2015.09.007
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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