Free energy computations identify the mutations required to confer trans-sialidase activity into Trypanosoma rangeli sialidase

Autores
Pierdominici Sottile, Gustavo; Palma, Juliana Isabel; Roitberg, Adrián
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Trypanosoma rangeli's sialidase (TrSA) and Trypanosoma cruzi's trans-sialidase (TcTS) are members of the glycoside hydrolase family 33 (GH-33). They share 70% of sequence identity and their crystallographic Cα RMSD is 0.59 Å. Despite these similarities they catalyze different reactions. TcTS transfers sialic acid between glycoconjugates while TrSA can only cleave sialic acid from sialyl-glyconjugates. Significant effort has been invested into unraveling the differences between TrSA and TcTS, and into conferring TrSA with trans-sialidase activity through appropriate point mutations. Recently, we calculated the free-energy change for the formation of the covalent intermediate (CI) in TcTS and performed an energy decomposition analysis of that process. In this article we present a similar study for the formation of the CI in TrSA, as well as in a quintuple mutant (TrSA5mut), which has faint trans-sialidase activity. The comparison of these new results with those previously obtained for TcTS allowed identifying five extra mutations to be introduced in TrSA5mut that should create a mutant (TrSA10mut) with high trans-sialidase activity.
Fil: Pierdominici Sottile, Gustavo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Palma, Juliana Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Roitberg, Adrián. University of Florida. Departament of Chemistry; Estados Unidos
Materia
Molecular Dynamics
Trans-Sialidase
Sialidase
Computational Protein Engineering
Function-Changing Mutants
Free Energy
Qmmm
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:11336/33065
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/33065
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Free energy computations identify the mutations required to confer trans-sialidase activity into Trypanosoma rangeli sialidasePierdominici Sottile, GustavoPalma, Juliana IsabelRoitberg, AdriánMolecular DynamicsTrans-SialidaseSialidaseComputational Protein EngineeringFunction-Changing MutantsFree EnergyQmmmhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Trypanosoma rangeli's sialidase (TrSA) and Trypanosoma cruzi's trans-sialidase (TcTS) are members of the glycoside hydrolase family 33 (GH-33). They share 70% of sequence identity and their crystallographic Cα RMSD is 0.59 Å. Despite these similarities they catalyze different reactions. TcTS transfers sialic acid between glycoconjugates while TrSA can only cleave sialic acid from sialyl-glyconjugates. Significant effort has been invested into unraveling the differences between TrSA and TcTS, and into conferring TrSA with trans-sialidase activity through appropriate point mutations. Recently, we calculated the free-energy change for the formation of the covalent intermediate (CI) in TcTS and performed an energy decomposition analysis of that process. In this article we present a similar study for the formation of the CI in TrSA, as well as in a quintuple mutant (TrSA5mut), which has faint trans-sialidase activity. The comparison of these new results with those previously obtained for TcTS allowed identifying five extra mutations to be introduced in TrSA5mut that should create a mutant (TrSA10mut) with high trans-sialidase activity.Fil: Pierdominici Sottile, Gustavo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Palma, Juliana Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Roitberg, Adrián. University of Florida. Departament of Chemistry; Estados UnidosWiley2013-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/33065Roitberg, Adrián; Palma, Juliana Isabel; Pierdominici Sottile, Gustavo; Free energy computations identify the mutations required to confer trans-sialidase activity into Trypanosoma rangeli sialidase; Wiley; Proteins: Structure, Function And Genetics; 82; 3; 10-2013; 424-4350887-3585CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/prot.24408/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1002/prot.24408info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:03:53Zoai:ri.conicet.gov.ar:11336/33065instacron: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:34982025-09-29 10:03:53.94CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Free energy computations identify the mutations required to confer trans-sialidase activity into Trypanosoma rangeli sialidase
title Free energy computations identify the mutations required to confer trans-sialidase activity into Trypanosoma rangeli sialidase
spellingShingle Free energy computations identify the mutations required to confer trans-sialidase activity into Trypanosoma rangeli sialidase
Pierdominici Sottile, Gustavo
Molecular Dynamics
Trans-Sialidase
Sialidase
Computational Protein Engineering
Function-Changing Mutants
Free Energy
Qmmm
title_short Free energy computations identify the mutations required to confer trans-sialidase activity into Trypanosoma rangeli sialidase
title_full Free energy computations identify the mutations required to confer trans-sialidase activity into Trypanosoma rangeli sialidase
title_fullStr Free energy computations identify the mutations required to confer trans-sialidase activity into Trypanosoma rangeli sialidase
title_full_unstemmed Free energy computations identify the mutations required to confer trans-sialidase activity into Trypanosoma rangeli sialidase
title_sort Free energy computations identify the mutations required to confer trans-sialidase activity into Trypanosoma rangeli sialidase
dc.creator.none.fl_str_mv Pierdominici Sottile, Gustavo
Palma, Juliana Isabel
Roitberg, Adrián
author Pierdominici Sottile, Gustavo
author_facet Pierdominici Sottile, Gustavo
Palma, Juliana Isabel
Roitberg, Adrián
author_role author
author2 Palma, Juliana Isabel
Roitberg, Adrián
author2_role author
author
dc.subject.none.fl_str_mv Molecular Dynamics
Trans-Sialidase
Sialidase
Computational Protein Engineering
Function-Changing Mutants
Free Energy
Qmmm
topic Molecular Dynamics
Trans-Sialidase
Sialidase
Computational Protein Engineering
Function-Changing Mutants
Free Energy
Qmmm
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Trypanosoma rangeli's sialidase (TrSA) and Trypanosoma cruzi's trans-sialidase (TcTS) are members of the glycoside hydrolase family 33 (GH-33). They share 70% of sequence identity and their crystallographic Cα RMSD is 0.59 Å. Despite these similarities they catalyze different reactions. TcTS transfers sialic acid between glycoconjugates while TrSA can only cleave sialic acid from sialyl-glyconjugates. Significant effort has been invested into unraveling the differences between TrSA and TcTS, and into conferring TrSA with trans-sialidase activity through appropriate point mutations. Recently, we calculated the free-energy change for the formation of the covalent intermediate (CI) in TcTS and performed an energy decomposition analysis of that process. In this article we present a similar study for the formation of the CI in TrSA, as well as in a quintuple mutant (TrSA5mut), which has faint trans-sialidase activity. The comparison of these new results with those previously obtained for TcTS allowed identifying five extra mutations to be introduced in TrSA5mut that should create a mutant (TrSA10mut) with high trans-sialidase activity.
Fil: Pierdominici Sottile, Gustavo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Palma, Juliana Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Roitberg, Adrián. University of Florida. Departament of Chemistry; Estados Unidos
description Trypanosoma rangeli's sialidase (TrSA) and Trypanosoma cruzi's trans-sialidase (TcTS) are members of the glycoside hydrolase family 33 (GH-33). They share 70% of sequence identity and their crystallographic Cα RMSD is 0.59 Å. Despite these similarities they catalyze different reactions. TcTS transfers sialic acid between glycoconjugates while TrSA can only cleave sialic acid from sialyl-glyconjugates. Significant effort has been invested into unraveling the differences between TrSA and TcTS, and into conferring TrSA with trans-sialidase activity through appropriate point mutations. Recently, we calculated the free-energy change for the formation of the covalent intermediate (CI) in TcTS and performed an energy decomposition analysis of that process. In this article we present a similar study for the formation of the CI in TrSA, as well as in a quintuple mutant (TrSA5mut), which has faint trans-sialidase activity. The comparison of these new results with those previously obtained for TcTS allowed identifying five extra mutations to be introduced in TrSA5mut that should create a mutant (TrSA10mut) with high trans-sialidase activity.
publishDate 2013
dc.date.none.fl_str_mv 2013-10
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/11336/33065
Roitberg, Adrián; Palma, Juliana Isabel; Pierdominici Sottile, Gustavo; Free energy computations identify the mutations required to confer trans-sialidase activity into Trypanosoma rangeli sialidase; Wiley; Proteins: Structure, Function And Genetics; 82; 3; 10-2013; 424-435
0887-3585
CONICET Digital
CONICET
url http://hdl.handle.net/11336/33065
identifier_str_mv Roitberg, Adrián; Palma, Juliana Isabel; Pierdominici Sottile, Gustavo; Free energy computations identify the mutations required to confer trans-sialidase activity into Trypanosoma rangeli sialidase; Wiley; Proteins: Structure, Function And Genetics; 82; 3; 10-2013; 424-435
0887-3585
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/prot.24408/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1002/prot.24408
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
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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 13.069144

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