Toward the discovery of inhibitors of babesipain-1, a Babesia bigemina cysteine protease: in vitro evaluation, homology modeling and molecular docking studies
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://repositorio-aberto.up.pt/handle/10216/82131 |
Resumo: | Babesia bigemina is a protozoan parasite that causes babesiosis, a disease with a world-wide distribution in mammals, principally affecting cattle and man. The unveiling of the genome of B. bigemina is a project in active progress that has already revealed a number of new targets with potential interest for the design of anti-babesiosis drugs. In this context, babesipain-1 has been identified as a proteolytically active enzyme whose three-dimensional structure has not been resolved yet, but which is known to be inhibited by cysteine proteases inhibitors such as E64, ALLN, leupeptin, and vinyl sulfones. In this work, we introduce (1) a homology model of babesipain-1; (2) a comparison between babesipain-1 and falcipain-2, a cysteine protease of the malaria parasite Plasmodium falciparum; (3) in vitro data for babesipain-1 inhibition by HEDICINs and HECINs, previously reported as modest inhibitors of falcipain-2; and (4) the docked binding conformations of HEDICINs and HECINs in the model of babesipain-1. HEDICINs presented similar preferred binding conformations for both babesipain-1 and falcipain-2. However, in vitro bioassay shows that HEDICINs and HECINs are better inhibitors of babesipain-1 than of falcipain-2, which could be explained by observed differences between the active pockets of these proteins in silico. Results presented herein provide a valuable contribution to future computer-aided molecular design of new babesipain-1 inhibitors. |
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Toward the discovery of inhibitors of babesipain-1, a Babesia bigemina cysteine protease: in vitro evaluation, homology modeling and molecular docking studiesCiências da computação e da informaçãoComputer and information sciencesBabesia bigemina is a protozoan parasite that causes babesiosis, a disease with a world-wide distribution in mammals, principally affecting cattle and man. The unveiling of the genome of B. bigemina is a project in active progress that has already revealed a number of new targets with potential interest for the design of anti-babesiosis drugs. In this context, babesipain-1 has been identified as a proteolytically active enzyme whose three-dimensional structure has not been resolved yet, but which is known to be inhibited by cysteine proteases inhibitors such as E64, ALLN, leupeptin, and vinyl sulfones. In this work, we introduce (1) a homology model of babesipain-1; (2) a comparison between babesipain-1 and falcipain-2, a cysteine protease of the malaria parasite Plasmodium falciparum; (3) in vitro data for babesipain-1 inhibition by HEDICINs and HECINs, previously reported as modest inhibitors of falcipain-2; and (4) the docked binding conformations of HEDICINs and HECINs in the model of babesipain-1. HEDICINs presented similar preferred binding conformations for both babesipain-1 and falcipain-2. However, in vitro bioassay shows that HEDICINs and HECINs are better inhibitors of babesipain-1 than of falcipain-2, which could be explained by observed differences between the active pockets of these proteins in silico. Results presented herein provide a valuable contribution to future computer-aided molecular design of new babesipain-1 inhibitors.20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://repositorio-aberto.up.pt/handle/10216/82131eng0920-654X10.1007/s10822-013-9682-2Bianca PerezSandra AntunesLidia M GoncalvesAna DomingosJose R B GomesPaula GomesCatia Teixeirainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T14:30:22Zoai:repositorio-aberto.up.pt:10216/82131Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:02:43.157248Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Toward the discovery of inhibitors of babesipain-1, a Babesia bigemina cysteine protease: in vitro evaluation, homology modeling and molecular docking studies |
title |
Toward the discovery of inhibitors of babesipain-1, a Babesia bigemina cysteine protease: in vitro evaluation, homology modeling and molecular docking studies |
spellingShingle |
Toward the discovery of inhibitors of babesipain-1, a Babesia bigemina cysteine protease: in vitro evaluation, homology modeling and molecular docking studies Bianca Perez Ciências da computação e da informação Computer and information sciences |
title_short |
Toward the discovery of inhibitors of babesipain-1, a Babesia bigemina cysteine protease: in vitro evaluation, homology modeling and molecular docking studies |
title_full |
Toward the discovery of inhibitors of babesipain-1, a Babesia bigemina cysteine protease: in vitro evaluation, homology modeling and molecular docking studies |
title_fullStr |
Toward the discovery of inhibitors of babesipain-1, a Babesia bigemina cysteine protease: in vitro evaluation, homology modeling and molecular docking studies |
title_full_unstemmed |
Toward the discovery of inhibitors of babesipain-1, a Babesia bigemina cysteine protease: in vitro evaluation, homology modeling and molecular docking studies |
title_sort |
Toward the discovery of inhibitors of babesipain-1, a Babesia bigemina cysteine protease: in vitro evaluation, homology modeling and molecular docking studies |
author |
Bianca Perez |
author_facet |
Bianca Perez Sandra Antunes Lidia M Goncalves Ana Domingos Jose R B Gomes Paula Gomes Catia Teixeira |
author_role |
author |
author2 |
Sandra Antunes Lidia M Goncalves Ana Domingos Jose R B Gomes Paula Gomes Catia Teixeira |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Bianca Perez Sandra Antunes Lidia M Goncalves Ana Domingos Jose R B Gomes Paula Gomes Catia Teixeira |
dc.subject.por.fl_str_mv |
Ciências da computação e da informação Computer and information sciences |
topic |
Ciências da computação e da informação Computer and information sciences |
description |
Babesia bigemina is a protozoan parasite that causes babesiosis, a disease with a world-wide distribution in mammals, principally affecting cattle and man. The unveiling of the genome of B. bigemina is a project in active progress that has already revealed a number of new targets with potential interest for the design of anti-babesiosis drugs. In this context, babesipain-1 has been identified as a proteolytically active enzyme whose three-dimensional structure has not been resolved yet, but which is known to be inhibited by cysteine proteases inhibitors such as E64, ALLN, leupeptin, and vinyl sulfones. In this work, we introduce (1) a homology model of babesipain-1; (2) a comparison between babesipain-1 and falcipain-2, a cysteine protease of the malaria parasite Plasmodium falciparum; (3) in vitro data for babesipain-1 inhibition by HEDICINs and HECINs, previously reported as modest inhibitors of falcipain-2; and (4) the docked binding conformations of HEDICINs and HECINs in the model of babesipain-1. HEDICINs presented similar preferred binding conformations for both babesipain-1 and falcipain-2. However, in vitro bioassay shows that HEDICINs and HECINs are better inhibitors of babesipain-1 than of falcipain-2, which could be explained by observed differences between the active pockets of these proteins in silico. Results presented herein provide a valuable contribution to future computer-aided molecular design of new babesipain-1 inhibitors. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013 2013-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio-aberto.up.pt/handle/10216/82131 |
url |
https://repositorio-aberto.up.pt/handle/10216/82131 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0920-654X 10.1007/s10822-013-9682-2 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799135952028827649 |