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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/33065
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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 Técnicas2025-09-03T09:57:36Zoai: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:34982025-09-03 09:57:37.192CONICET 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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1842269472453296128 |
score |
13.13397 |