Unraveling the Differences of the Hydrolytic Activity of Trypanosoma cruzi trans-Sialidase and Trypanosoma rangeli Sialidase: A Quantum Mechanics–Molecular Mechanics Modeling Study...

Autores
Bueren Calabuig, Juan A.; Pierdominici Sottile, Gustavo; Roitberg, Adrián
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chagas’ disease, also known as American trypanosomiasis, is a lethal, chronic disease that currently affects more than 10 million people in Central and South America. The trans-sialidase from Trypanosoma cruzi (T. cruzi, TcTS) is a crucial enzyme for the survival of this parasite: sialic acids from the host are transferred to the cell surface glycoproteins of the trypanosome, thereby evading the host’s immune system. On the other hand, the sialidase of T. rangeli (TrSA), which shares 70% sequence identity with TcTS, is a strict hydrolase and shows no trans-sialidase activity. Therefore, TcTS and TrSA represent an excellent framework to understand how different catalytic activities can be achieved with extremely similar structures. By means of combined quantum mechanics–molecular mechanics (QM/MM, SCC-DFTB/Amberff99SB) calculations and umbrella sampling simulations, we investigated the hydrolysis mechanisms of TcTS and TrSA and computed the free energy profiles of these reactions. The results, together with our previous computational investigations, are able to explain the catalytic mechanism of sialidases and describe how subtle differences in the active site make TrSA a strict hydrolase and TcTS a more efficient trans-sialidase.
Fil: Bueren Calabuig, Juan A.. University of Florida; Estados Unidos
Fil: Pierdominici Sottile, Gustavo. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Roitberg, Adrián. University of Florida; Estados Unidos
Materia
QMMM
UMBRELLA
CATALYSIS
SIALIDASE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/33742
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Unraveling the Differences of the Hydrolytic Activity of Trypanosoma cruzi trans-Sialidase and Trypanosoma rangeli Sialidase: A Quantum Mechanics–Molecular Mechanics Modeling StudyBueren Calabuig, Juan A.Pierdominici Sottile, GustavoRoitberg, AdriánQMMMUMBRELLACATALYSISSIALIDASEhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Chagas’ disease, also known as American trypanosomiasis, is a lethal, chronic disease that currently affects more than 10 million people in Central and South America. The trans-sialidase from Trypanosoma cruzi (T. cruzi, TcTS) is a crucial enzyme for the survival of this parasite: sialic acids from the host are transferred to the cell surface glycoproteins of the trypanosome, thereby evading the host’s immune system. On the other hand, the sialidase of T. rangeli (TrSA), which shares 70% sequence identity with TcTS, is a strict hydrolase and shows no trans-sialidase activity. Therefore, TcTS and TrSA represent an excellent framework to understand how different catalytic activities can be achieved with extremely similar structures. By means of combined quantum mechanics–molecular mechanics (QM/MM, SCC-DFTB/Amberff99SB) calculations and umbrella sampling simulations, we investigated the hydrolysis mechanisms of TcTS and TrSA and computed the free energy profiles of these reactions. The results, together with our previous computational investigations, are able to explain the catalytic mechanism of sialidases and describe how subtle differences in the active site make TrSA a strict hydrolase and TcTS a more efficient trans-sialidase.Fil: Bueren Calabuig, Juan A.. University of Florida; Estados UnidosFil: Pierdominici Sottile, Gustavo. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roitberg, Adrián. University of Florida; Estados UnidosAmerican Chemical Society2014-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/zipapplication/pdfhttp://hdl.handle.net/11336/33742Bueren Calabuig, Juan A.; Pierdominici Sottile, Gustavo; Roitberg, Adrián; Unraveling the Differences of the Hydrolytic Activity of Trypanosoma cruzi trans-Sialidase and Trypanosoma rangeli Sialidase: A Quantum Mechanics–Molecular Mechanics Modeling Study; American Chemical Society; Journal of Physical Chemistry B; 118; 22; 5-2014; 5807-58161520-6106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/10.1021/jp412294rinfo:eu-repo/semantics/altIdentifier/doi/ 10.1021/jp412294rinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051249/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:15:19Zoai:ri.conicet.gov.ar:11336/33742instacron: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 10:15:19.675CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Unraveling the Differences of the Hydrolytic Activity of Trypanosoma cruzi trans-Sialidase and Trypanosoma rangeli Sialidase: A Quantum Mechanics–Molecular Mechanics Modeling Study
title Unraveling the Differences of the Hydrolytic Activity of Trypanosoma cruzi trans-Sialidase and Trypanosoma rangeli Sialidase: A Quantum Mechanics–Molecular Mechanics Modeling Study
spellingShingle Unraveling the Differences of the Hydrolytic Activity of Trypanosoma cruzi trans-Sialidase and Trypanosoma rangeli Sialidase: A Quantum Mechanics–Molecular Mechanics Modeling Study
Bueren Calabuig, Juan A.
QMMM
UMBRELLA
CATALYSIS
SIALIDASE
title_short Unraveling the Differences of the Hydrolytic Activity of Trypanosoma cruzi trans-Sialidase and Trypanosoma rangeli Sialidase: A Quantum Mechanics–Molecular Mechanics Modeling Study
title_full Unraveling the Differences of the Hydrolytic Activity of Trypanosoma cruzi trans-Sialidase and Trypanosoma rangeli Sialidase: A Quantum Mechanics–Molecular Mechanics Modeling Study
title_fullStr Unraveling the Differences of the Hydrolytic Activity of Trypanosoma cruzi trans-Sialidase and Trypanosoma rangeli Sialidase: A Quantum Mechanics–Molecular Mechanics Modeling Study
title_full_unstemmed Unraveling the Differences of the Hydrolytic Activity of Trypanosoma cruzi trans-Sialidase and Trypanosoma rangeli Sialidase: A Quantum Mechanics–Molecular Mechanics Modeling Study
title_sort Unraveling the Differences of the Hydrolytic Activity of Trypanosoma cruzi trans-Sialidase and Trypanosoma rangeli Sialidase: A Quantum Mechanics–Molecular Mechanics Modeling Study
dc.creator.none.fl_str_mv Bueren Calabuig, Juan A.
Pierdominici Sottile, Gustavo
Roitberg, Adrián
author Bueren Calabuig, Juan A.
author_facet Bueren Calabuig, Juan A.
Pierdominici Sottile, Gustavo
Roitberg, Adrián
author_role author
author2 Pierdominici Sottile, Gustavo
Roitberg, Adrián
author2_role author
author
dc.subject.none.fl_str_mv QMMM
UMBRELLA
CATALYSIS
SIALIDASE
topic QMMM
UMBRELLA
CATALYSIS
SIALIDASE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chagas’ disease, also known as American trypanosomiasis, is a lethal, chronic disease that currently affects more than 10 million people in Central and South America. The trans-sialidase from Trypanosoma cruzi (T. cruzi, TcTS) is a crucial enzyme for the survival of this parasite: sialic acids from the host are transferred to the cell surface glycoproteins of the trypanosome, thereby evading the host’s immune system. On the other hand, the sialidase of T. rangeli (TrSA), which shares 70% sequence identity with TcTS, is a strict hydrolase and shows no trans-sialidase activity. Therefore, TcTS and TrSA represent an excellent framework to understand how different catalytic activities can be achieved with extremely similar structures. By means of combined quantum mechanics–molecular mechanics (QM/MM, SCC-DFTB/Amberff99SB) calculations and umbrella sampling simulations, we investigated the hydrolysis mechanisms of TcTS and TrSA and computed the free energy profiles of these reactions. The results, together with our previous computational investigations, are able to explain the catalytic mechanism of sialidases and describe how subtle differences in the active site make TrSA a strict hydrolase and TcTS a more efficient trans-sialidase.
Fil: Bueren Calabuig, Juan A.. University of Florida; Estados Unidos
Fil: Pierdominici Sottile, Gustavo. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Roitberg, Adrián. University of Florida; Estados Unidos
description Chagas’ disease, also known as American trypanosomiasis, is a lethal, chronic disease that currently affects more than 10 million people in Central and South America. The trans-sialidase from Trypanosoma cruzi (T. cruzi, TcTS) is a crucial enzyme for the survival of this parasite: sialic acids from the host are transferred to the cell surface glycoproteins of the trypanosome, thereby evading the host’s immune system. On the other hand, the sialidase of T. rangeli (TrSA), which shares 70% sequence identity with TcTS, is a strict hydrolase and shows no trans-sialidase activity. Therefore, TcTS and TrSA represent an excellent framework to understand how different catalytic activities can be achieved with extremely similar structures. By means of combined quantum mechanics–molecular mechanics (QM/MM, SCC-DFTB/Amberff99SB) calculations and umbrella sampling simulations, we investigated the hydrolysis mechanisms of TcTS and TrSA and computed the free energy profiles of these reactions. The results, together with our previous computational investigations, are able to explain the catalytic mechanism of sialidases and describe how subtle differences in the active site make TrSA a strict hydrolase and TcTS a more efficient trans-sialidase.
publishDate 2014
dc.date.none.fl_str_mv 2014-05
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/11336/33742
Bueren Calabuig, Juan A.; Pierdominici Sottile, Gustavo; Roitberg, Adrián; Unraveling the Differences of the Hydrolytic Activity of Trypanosoma cruzi trans-Sialidase and Trypanosoma rangeli Sialidase: A Quantum Mechanics–Molecular Mechanics Modeling Study; American Chemical Society; Journal of Physical Chemistry B; 118; 22; 5-2014; 5807-5816
1520-6106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/33742
identifier_str_mv Bueren Calabuig, Juan A.; Pierdominici Sottile, Gustavo; Roitberg, Adrián; Unraveling the Differences of the Hydrolytic Activity of Trypanosoma cruzi trans-Sialidase and Trypanosoma rangeli Sialidase: A Quantum Mechanics–Molecular Mechanics Modeling Study; American Chemical Society; Journal of Physical Chemistry B; 118; 22; 5-2014; 5807-5816
1520-6106
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://pubs.acs.org/doi/10.1021/jp412294r
info:eu-repo/semantics/altIdentifier/doi/ 10.1021/jp412294r
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051249/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/zip
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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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