Estudos in vitro e de modelagem molecular in silico aplicados à interação entre a enzima delta-aminolevulinato desidratase e metais do grupo 10 (níquel, paládio e platina) e 11 (cobre, prata e ouro) da tabela periódica
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/18220 |
Resumo: | Mammalian δ- aminolevulinate dehydratase (δ-ALA-D) is a metalloenzyme, which requires Zn(II) and reduced thiol groups for maximal catalytic activity, and is an important molecular target for the widespread environmental toxic metals. The mechanism underlying the δ-ALA-D inhibition by elements of Group 10 nickel (NiCl2), palladium (PdCl2), platinum (PtCl2 and PtCl4) and 11 cupper (CuSO4), silver (AgNO3), glod (AuCl3) of periodic table has not yet been determined. The main objective of the present study was to characterize the molecular mechanism of δ-ALA-D inhibition caused by salts of elements of Group 10 and 11 using in vitro (δ-ALA-D activity in human erythrocytes) and in silico (by geometry optimization with the program MOPAC20122 - PM6 method). Our results showed that Ni(II) and Pd(II) caused only a small inhibition (~ 10%) in the δ-ALA-D enzyme activity, and this inhibition was blunted by Zn(II). Pt forms significantly inhibited the enzymatic activity of δ- ALA-D (75% and 44%, respectively), but this inhibition was attenuated by Zn (II) and DTT, indicating that when moved the element most light to the heavier component, tends to change inhibition in a competition for Zn (II) for the oxidation of thiols. In group 11, all metals inhibited δ-ALA-D, and in accordance with data in vitro and in silico the mechanism of inhibition seems to be related to the oxidation of thiol groups of the active site, while incubation with Zn (II) appears to block the inhibitory mechanism of the metals of the group 11 for protecting the active enzyme. |
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Estudos in vitro e de modelagem molecular in silico aplicados à interação entre a enzima delta-aminolevulinato desidratase e metais do grupo 10 (níquel, paládio e platina) e 11 (cobre, prata e ouro) da tabela periódicaStudies in vitro and molecular modeling in silico applied to the interaction between enzyme deltaaminolevulinate dehydratase and metals group 10 (nickel, palladium and platinum) and 11 (copper, silver and gold) the periodic tableδ-aminolevulinato desidrataseNiquelPaládioPlatinaCobrePrataOuroSítio ativoGrupos tióisZincoδ-aminolevulinic acid dehydrataseNickelPalladiumPlatinumCopperSilverGoldActive siteThiol groupsZincCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAMammalian δ- aminolevulinate dehydratase (δ-ALA-D) is a metalloenzyme, which requires Zn(II) and reduced thiol groups for maximal catalytic activity, and is an important molecular target for the widespread environmental toxic metals. The mechanism underlying the δ-ALA-D inhibition by elements of Group 10 nickel (NiCl2), palladium (PdCl2), platinum (PtCl2 and PtCl4) and 11 cupper (CuSO4), silver (AgNO3), glod (AuCl3) of periodic table has not yet been determined. The main objective of the present study was to characterize the molecular mechanism of δ-ALA-D inhibition caused by salts of elements of Group 10 and 11 using in vitro (δ-ALA-D activity in human erythrocytes) and in silico (by geometry optimization with the program MOPAC20122 - PM6 method). Our results showed that Ni(II) and Pd(II) caused only a small inhibition (~ 10%) in the δ-ALA-D enzyme activity, and this inhibition was blunted by Zn(II). Pt forms significantly inhibited the enzymatic activity of δ- ALA-D (75% and 44%, respectively), but this inhibition was attenuated by Zn (II) and DTT, indicating that when moved the element most light to the heavier component, tends to change inhibition in a competition for Zn (II) for the oxidation of thiols. In group 11, all metals inhibited δ-ALA-D, and in accordance with data in vitro and in silico the mechanism of inhibition seems to be related to the oxidation of thiol groups of the active site, while incubation with Zn (II) appears to block the inhibitory mechanism of the metals of the group 11 for protecting the active enzyme.A enzima δ-aminolevulinato desidratase humana (δ-ALA-D) é uma metaloenzima que requer grupos tióis reduzidos e o metal Zn(II) para a atividade catalítica máxima, sendo consequentemente um alvo molecular importante para os metais tóxicos ambientais. Sendo assim, este estudo teve como objetivo caracterizar o mecanismo molecular de interação dos sais dos elementos do Grupo 10 niquel (NiCl2), paládio (PdCl2), platina (PtCl2 e PtCl4) e 11 cobre (CuSO4), prata (AgNO3), ouro (AuCl3) com o sítio ativo da δ-ALA-D, usando métodos in vitro (atividade da δ-ALA-D de eritrócitos humanos) e in silico (por optimização geométrica com o programa MOPAC20122 - método PM6). Nossos resultados mostraram que Ni(II) e Pd(II) causaram apenas uma pequena inibição (~10%) na atividade da δ-ALA-D de eritrócitos humanos, sendo que esta inibição foi revertida por Zn(II). Pt(II) e Pt(IV) inibiram significativamente a atividade enzimática da δ-ALA-D (75% E 44%, respectivamente) e oxidaram grupos tióis de cisteína e glutationa. A inibição causada na δ-ALA-D por estes metais foi atenuada por Zn (II) e DTT, indicando que à medida que avançamos do elemento mais leve para o elemento mais pesado, a inibição tende a mudar de uma competição por Zn(II) para oxidação de tióis. Já no grupo 11, todos os metais inibiram a enzima δ-ALA-D, e de acordo com dados in vitro e in silico o mecanismo de inibição parece estar relacionado com a oxidação dos grupos tióis do sítio ativo, enquanto que a incubação com Zn(II) parece bloquear o mecanismo inibitório dos metais do grupo 11 por proteger o sítio ativo da enzima.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasRocha, João Batista Teixeira dahttp://lattes.cnpq.br/3935055744673018Barbosa, Nilda Berenice de Vargashttp://lattes.cnpq.br/5901511067144019Pereira, Maria Esterhttp://lattes.cnpq.br/9299114496157799Pinton, Simonehttp://lattes.cnpq.br/1205982002582299Klimaczewski, Cláudia Vargas2019-09-12T19:26:08Z2019-09-12T19:26:08Z2014-08-05info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/18220porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2022-05-03T12:12:42Zoai:repositorio.ufsm.br:1/18220Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-05-03T12:12:42Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Estudos in vitro e de modelagem molecular in silico aplicados à interação entre a enzima delta-aminolevulinato desidratase e metais do grupo 10 (níquel, paládio e platina) e 11 (cobre, prata e ouro) da tabela periódica Studies in vitro and molecular modeling in silico applied to the interaction between enzyme deltaaminolevulinate dehydratase and metals group 10 (nickel, palladium and platinum) and 11 (copper, silver and gold) the periodic table |
title |
Estudos in vitro e de modelagem molecular in silico aplicados à interação entre a enzima delta-aminolevulinato desidratase e metais do grupo 10 (níquel, paládio e platina) e 11 (cobre, prata e ouro) da tabela periódica |
spellingShingle |
Estudos in vitro e de modelagem molecular in silico aplicados à interação entre a enzima delta-aminolevulinato desidratase e metais do grupo 10 (níquel, paládio e platina) e 11 (cobre, prata e ouro) da tabela periódica Klimaczewski, Cláudia Vargas δ-aminolevulinato desidratase Niquel Paládio Platina Cobre Prata Ouro Sítio ativo Grupos tióis Zinco δ-aminolevulinic acid dehydratase Nickel Palladium Platinum Copper Silver Gold Active site Thiol groups Zinc CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Estudos in vitro e de modelagem molecular in silico aplicados à interação entre a enzima delta-aminolevulinato desidratase e metais do grupo 10 (níquel, paládio e platina) e 11 (cobre, prata e ouro) da tabela periódica |
title_full |
Estudos in vitro e de modelagem molecular in silico aplicados à interação entre a enzima delta-aminolevulinato desidratase e metais do grupo 10 (níquel, paládio e platina) e 11 (cobre, prata e ouro) da tabela periódica |
title_fullStr |
Estudos in vitro e de modelagem molecular in silico aplicados à interação entre a enzima delta-aminolevulinato desidratase e metais do grupo 10 (níquel, paládio e platina) e 11 (cobre, prata e ouro) da tabela periódica |
title_full_unstemmed |
Estudos in vitro e de modelagem molecular in silico aplicados à interação entre a enzima delta-aminolevulinato desidratase e metais do grupo 10 (níquel, paládio e platina) e 11 (cobre, prata e ouro) da tabela periódica |
title_sort |
Estudos in vitro e de modelagem molecular in silico aplicados à interação entre a enzima delta-aminolevulinato desidratase e metais do grupo 10 (níquel, paládio e platina) e 11 (cobre, prata e ouro) da tabela periódica |
author |
Klimaczewski, Cláudia Vargas |
author_facet |
Klimaczewski, Cláudia Vargas |
author_role |
author |
dc.contributor.none.fl_str_mv |
Rocha, João Batista Teixeira da http://lattes.cnpq.br/3935055744673018 Barbosa, Nilda Berenice de Vargas http://lattes.cnpq.br/5901511067144019 Pereira, Maria Ester http://lattes.cnpq.br/9299114496157799 Pinton, Simone http://lattes.cnpq.br/1205982002582299 |
dc.contributor.author.fl_str_mv |
Klimaczewski, Cláudia Vargas |
dc.subject.por.fl_str_mv |
δ-aminolevulinato desidratase Niquel Paládio Platina Cobre Prata Ouro Sítio ativo Grupos tióis Zinco δ-aminolevulinic acid dehydratase Nickel Palladium Platinum Copper Silver Gold Active site Thiol groups Zinc CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
δ-aminolevulinato desidratase Niquel Paládio Platina Cobre Prata Ouro Sítio ativo Grupos tióis Zinco δ-aminolevulinic acid dehydratase Nickel Palladium Platinum Copper Silver Gold Active site Thiol groups Zinc CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Mammalian δ- aminolevulinate dehydratase (δ-ALA-D) is a metalloenzyme, which requires Zn(II) and reduced thiol groups for maximal catalytic activity, and is an important molecular target for the widespread environmental toxic metals. The mechanism underlying the δ-ALA-D inhibition by elements of Group 10 nickel (NiCl2), palladium (PdCl2), platinum (PtCl2 and PtCl4) and 11 cupper (CuSO4), silver (AgNO3), glod (AuCl3) of periodic table has not yet been determined. The main objective of the present study was to characterize the molecular mechanism of δ-ALA-D inhibition caused by salts of elements of Group 10 and 11 using in vitro (δ-ALA-D activity in human erythrocytes) and in silico (by geometry optimization with the program MOPAC20122 - PM6 method). Our results showed that Ni(II) and Pd(II) caused only a small inhibition (~ 10%) in the δ-ALA-D enzyme activity, and this inhibition was blunted by Zn(II). Pt forms significantly inhibited the enzymatic activity of δ- ALA-D (75% and 44%, respectively), but this inhibition was attenuated by Zn (II) and DTT, indicating that when moved the element most light to the heavier component, tends to change inhibition in a competition for Zn (II) for the oxidation of thiols. In group 11, all metals inhibited δ-ALA-D, and in accordance with data in vitro and in silico the mechanism of inhibition seems to be related to the oxidation of thiol groups of the active site, while incubation with Zn (II) appears to block the inhibitory mechanism of the metals of the group 11 for protecting the active enzyme. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-08-05 2019-09-12T19:26:08Z 2019-09-12T19:26:08Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/18220 |
url |
http://repositorio.ufsm.br/handle/1/18220 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1805922160860987392 |