Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury Compounds

Autores
Benchoam, Dayana; Cuevasanta, Ernesto; Julió Plana, Laia; Capece, Luciana; Banerjee, Ruma; Alvarez, Beatriz
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cystathionine β-synthase (CBS) is an enzyme involved in sulfur metabolism that catalyzes the pyridoxal phosphate-dependent condensation of homocysteine with serine or cysteine to form cystathionine and water or hydrogen sulfide (H2S), respectively. CBS possesses a b-type heme coordinated by histidine and cysteine. Fe(III)-CBS is inert toward exogenous ligands, while Fe(II)-CBS is reactive. Both Fe(III)-and Fe(II)-CBS are sensitive to mercury compounds. In this study, we describe the kinetics of the reactions with mercuric chloride (HgCl2) and p-chloromercuribenzoic acid. These reactions were multiphasic and resulted in five-coordinate CBS lacking thiolate ligation, with six-coordinate species as intermediates. Computational QM/MM studies supported the feasibility of formation of species in which the thiolate is proximal to both the iron ion and the mercury compound. The reactions of Fe(II)-CBS were faster than those of Fe(III)-CBS. The observed rate constants of the first phase increased hyperbolically with concentration of the mercury compounds, with limiting values of 0.3-0.4 s-1 for Fe(III)-CBS and 40 ± 4 s-1 for Fe(II)-CBS. The data were interpreted in terms of alternative models of conformational selection or induced fit. Exposure of Fe(III)-CBS to HgCl2 led to heme release and activity loss. Our study reveals the complexity of the interactions between mercury compounds and CBS.
Fil: Benchoam, Dayana. Universidad de la Republica; Uruguay
Fil: Cuevasanta, Ernesto. Universidad de la Republica; Uruguay
Fil: Julió Plana, Laia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Capece, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Banerjee, Ruma. University of Michigan; Estados Unidos
Fil: Alvarez, Beatriz. Universidad de la República; Uruguay
Materia
Cystathionine β‐Synthase
Mercury Compounds
Heme-Thiolate
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:11336/182213
Acceder
id CONICETDig_342d2715eb93f5fc2056defe7ea05515
oai_identifier_str oai:ri.conicet.gov.ar:11336/182213
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury CompoundsBenchoam, DayanaCuevasanta, ErnestoJulió Plana, LaiaCapece, LucianaBanerjee, RumaAlvarez, BeatrizCystathionine β‐SynthaseMercury CompoundsHeme-Thiolatehttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Cystathionine β-synthase (CBS) is an enzyme involved in sulfur metabolism that catalyzes the pyridoxal phosphate-dependent condensation of homocysteine with serine or cysteine to form cystathionine and water or hydrogen sulfide (H2S), respectively. CBS possesses a b-type heme coordinated by histidine and cysteine. Fe(III)-CBS is inert toward exogenous ligands, while Fe(II)-CBS is reactive. Both Fe(III)-and Fe(II)-CBS are sensitive to mercury compounds. In this study, we describe the kinetics of the reactions with mercuric chloride (HgCl2) and p-chloromercuribenzoic acid. These reactions were multiphasic and resulted in five-coordinate CBS lacking thiolate ligation, with six-coordinate species as intermediates. Computational QM/MM studies supported the feasibility of formation of species in which the thiolate is proximal to both the iron ion and the mercury compound. The reactions of Fe(II)-CBS were faster than those of Fe(III)-CBS. The observed rate constants of the first phase increased hyperbolically with concentration of the mercury compounds, with limiting values of 0.3-0.4 s-1 for Fe(III)-CBS and 40 ± 4 s-1 for Fe(II)-CBS. The data were interpreted in terms of alternative models of conformational selection or induced fit. Exposure of Fe(III)-CBS to HgCl2 led to heme release and activity loss. Our study reveals the complexity of the interactions between mercury compounds and CBS.Fil: Benchoam, Dayana. Universidad de la Republica; UruguayFil: Cuevasanta, Ernesto. Universidad de la Republica; UruguayFil: Julió Plana, Laia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Capece, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Banerjee, Ruma. University of Michigan; Estados UnidosFil: Alvarez, Beatriz. Universidad de la República; UruguayAmerican Chemical Society2021-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/182213Benchoam, Dayana; Cuevasanta, Ernesto; Julió Plana, Laia; Capece, Luciana; Banerjee, Ruma; et al.; Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury Compounds; American Chemical Society; ACS Omega; 6; 3; 1-2021; 2192-22052470-1343CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1021/acsomega.0c05475info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:07:35Zoai:ri.conicet.gov.ar:11336/182213instacron: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 11:07:36.223CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury Compounds
title Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury Compounds
spellingShingle Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury Compounds
Benchoam, Dayana
Cystathionine β‐Synthase
Mercury Compounds
Heme-Thiolate
title_short Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury Compounds
title_full Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury Compounds
title_fullStr Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury Compounds
title_full_unstemmed Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury Compounds
title_sort Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury Compounds
dc.creator.none.fl_str_mv Benchoam, Dayana
Cuevasanta, Ernesto
Julió Plana, Laia
Capece, Luciana
Banerjee, Ruma
Alvarez, Beatriz
author Benchoam, Dayana
author_facet Benchoam, Dayana
Cuevasanta, Ernesto
Julió Plana, Laia
Capece, Luciana
Banerjee, Ruma
Alvarez, Beatriz
author_role author
author2 Cuevasanta, Ernesto
Julió Plana, Laia
Capece, Luciana
Banerjee, Ruma
Alvarez, Beatriz
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cystathionine β‐Synthase
Mercury Compounds
Heme-Thiolate
topic Cystathionine β‐Synthase
Mercury Compounds
Heme-Thiolate
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cystathionine β-synthase (CBS) is an enzyme involved in sulfur metabolism that catalyzes the pyridoxal phosphate-dependent condensation of homocysteine with serine or cysteine to form cystathionine and water or hydrogen sulfide (H2S), respectively. CBS possesses a b-type heme coordinated by histidine and cysteine. Fe(III)-CBS is inert toward exogenous ligands, while Fe(II)-CBS is reactive. Both Fe(III)-and Fe(II)-CBS are sensitive to mercury compounds. In this study, we describe the kinetics of the reactions with mercuric chloride (HgCl2) and p-chloromercuribenzoic acid. These reactions were multiphasic and resulted in five-coordinate CBS lacking thiolate ligation, with six-coordinate species as intermediates. Computational QM/MM studies supported the feasibility of formation of species in which the thiolate is proximal to both the iron ion and the mercury compound. The reactions of Fe(II)-CBS were faster than those of Fe(III)-CBS. The observed rate constants of the first phase increased hyperbolically with concentration of the mercury compounds, with limiting values of 0.3-0.4 s-1 for Fe(III)-CBS and 40 ± 4 s-1 for Fe(II)-CBS. The data were interpreted in terms of alternative models of conformational selection or induced fit. Exposure of Fe(III)-CBS to HgCl2 led to heme release and activity loss. Our study reveals the complexity of the interactions between mercury compounds and CBS.
Fil: Benchoam, Dayana. Universidad de la Republica; Uruguay
Fil: Cuevasanta, Ernesto. Universidad de la Republica; Uruguay
Fil: Julió Plana, Laia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Capece, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Banerjee, Ruma. University of Michigan; Estados Unidos
Fil: Alvarez, Beatriz. Universidad de la República; Uruguay
description Cystathionine β-synthase (CBS) is an enzyme involved in sulfur metabolism that catalyzes the pyridoxal phosphate-dependent condensation of homocysteine with serine or cysteine to form cystathionine and water or hydrogen sulfide (H2S), respectively. CBS possesses a b-type heme coordinated by histidine and cysteine. Fe(III)-CBS is inert toward exogenous ligands, while Fe(II)-CBS is reactive. Both Fe(III)-and Fe(II)-CBS are sensitive to mercury compounds. In this study, we describe the kinetics of the reactions with mercuric chloride (HgCl2) and p-chloromercuribenzoic acid. These reactions were multiphasic and resulted in five-coordinate CBS lacking thiolate ligation, with six-coordinate species as intermediates. Computational QM/MM studies supported the feasibility of formation of species in which the thiolate is proximal to both the iron ion and the mercury compound. The reactions of Fe(II)-CBS were faster than those of Fe(III)-CBS. The observed rate constants of the first phase increased hyperbolically with concentration of the mercury compounds, with limiting values of 0.3-0.4 s-1 for Fe(III)-CBS and 40 ± 4 s-1 for Fe(II)-CBS. The data were interpreted in terms of alternative models of conformational selection or induced fit. Exposure of Fe(III)-CBS to HgCl2 led to heme release and activity loss. Our study reveals the complexity of the interactions between mercury compounds and CBS.
publishDate 2021
dc.date.none.fl_str_mv 2021-01
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/11336/182213
Benchoam, Dayana; Cuevasanta, Ernesto; Julió Plana, Laia; Capece, Luciana; Banerjee, Ruma; et al.; Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury Compounds; American Chemical Society; ACS Omega; 6; 3; 1-2021; 2192-2205
2470-1343
CONICET Digital
CONICET
url http://hdl.handle.net/11336/182213
identifier_str_mv Benchoam, Dayana; Cuevasanta, Ernesto; Julió Plana, Laia; Capece, Luciana; Banerjee, Ruma; et al.; Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury Compounds; American Chemical Society; ACS Omega; 6; 3; 1-2021; 2192-2205
2470-1343
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/acsomega.0c05475
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 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 12.982451

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