CRYSTAL STRUCTURE OF BONE MARROW TYROSINE KINASE FROM CHROMOSOME X WITH COVALENT LIGANDS
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/70422 |
Resumo: | "Bone marrow tyrosine kinase in chromosome X (BMX) is a major member of the TEC family kinases and has been implicated in tumorigenecity, motility, proliferation and differentiation. BMX is highly overexpressed in prostate cancer and it is involved in the adaptive compensatory mechanism of castrate-resistance prostate cancer to androgen deprivation therapy. Besides, it suppresses a core component of the intrinsic apoptotic pathway, granting tumor cells the ability to escape apoptosis induced by chemotherapeutic drugs. BMX knockout mouse have a normal lifespan, without an obvious altered phenotype, suggesting that therapies based on BMX inhibition, may have limited side effects. We developed a series of BMX-IN-1 analogues that showed an increased inhibitory capacity when compared to BMX-IN-1. Since crystallographic information is essential to understand the molecular basis of BMX inhibition by covalent inhibitors we establish a baculovirus-insect expression system protocol for the production of the recombinant human BMX. Here we report the full biochemical and biophysical characterization of human BMX alone and in complex with different covalent ligands.(...)" |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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CRYSTAL STRUCTURE OF BONE MARROW TYROSINE KINASE FROM CHROMOSOME X WITH COVALENT LIGANDShuman recombinant BMXbaculovirus-insect expression vector systemcovalent bindersbiochemical and biophysical assaysX-ray crystallography structure determination"Bone marrow tyrosine kinase in chromosome X (BMX) is a major member of the TEC family kinases and has been implicated in tumorigenecity, motility, proliferation and differentiation. BMX is highly overexpressed in prostate cancer and it is involved in the adaptive compensatory mechanism of castrate-resistance prostate cancer to androgen deprivation therapy. Besides, it suppresses a core component of the intrinsic apoptotic pathway, granting tumor cells the ability to escape apoptosis induced by chemotherapeutic drugs. BMX knockout mouse have a normal lifespan, without an obvious altered phenotype, suggesting that therapies based on BMX inhibition, may have limited side effects. We developed a series of BMX-IN-1 analogues that showed an increased inhibitory capacity when compared to BMX-IN-1. Since crystallographic information is essential to understand the molecular basis of BMX inhibition by covalent inhibitors we establish a baculovirus-insect expression system protocol for the production of the recombinant human BMX. Here we report the full biochemical and biophysical characterization of human BMX alone and in complex with different covalent ligands.(...)"Matias, PedroRUNSousa, Bárbara Beatriz da Costa Botelho2021-09-30T00:30:25Z20182018-092018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/70422enginfo: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:RCAAP2024-03-11T04:33:22Zoai:run.unl.pt:10362/70422Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:35:06.020332Repositório 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 |
CRYSTAL STRUCTURE OF BONE MARROW TYROSINE KINASE FROM CHROMOSOME X WITH COVALENT LIGANDS |
title |
CRYSTAL STRUCTURE OF BONE MARROW TYROSINE KINASE FROM CHROMOSOME X WITH COVALENT LIGANDS |
spellingShingle |
CRYSTAL STRUCTURE OF BONE MARROW TYROSINE KINASE FROM CHROMOSOME X WITH COVALENT LIGANDS Sousa, Bárbara Beatriz da Costa Botelho human recombinant BMX baculovirus-insect expression vector system covalent binders biochemical and biophysical assays X-ray crystallography structure determination |
title_short |
CRYSTAL STRUCTURE OF BONE MARROW TYROSINE KINASE FROM CHROMOSOME X WITH COVALENT LIGANDS |
title_full |
CRYSTAL STRUCTURE OF BONE MARROW TYROSINE KINASE FROM CHROMOSOME X WITH COVALENT LIGANDS |
title_fullStr |
CRYSTAL STRUCTURE OF BONE MARROW TYROSINE KINASE FROM CHROMOSOME X WITH COVALENT LIGANDS |
title_full_unstemmed |
CRYSTAL STRUCTURE OF BONE MARROW TYROSINE KINASE FROM CHROMOSOME X WITH COVALENT LIGANDS |
title_sort |
CRYSTAL STRUCTURE OF BONE MARROW TYROSINE KINASE FROM CHROMOSOME X WITH COVALENT LIGANDS |
author |
Sousa, Bárbara Beatriz da Costa Botelho |
author_facet |
Sousa, Bárbara Beatriz da Costa Botelho |
author_role |
author |
dc.contributor.none.fl_str_mv |
Matias, Pedro RUN |
dc.contributor.author.fl_str_mv |
Sousa, Bárbara Beatriz da Costa Botelho |
dc.subject.por.fl_str_mv |
human recombinant BMX baculovirus-insect expression vector system covalent binders biochemical and biophysical assays X-ray crystallography structure determination |
topic |
human recombinant BMX baculovirus-insect expression vector system covalent binders biochemical and biophysical assays X-ray crystallography structure determination |
description |
"Bone marrow tyrosine kinase in chromosome X (BMX) is a major member of the TEC family kinases and has been implicated in tumorigenecity, motility, proliferation and differentiation. BMX is highly overexpressed in prostate cancer and it is involved in the adaptive compensatory mechanism of castrate-resistance prostate cancer to androgen deprivation therapy. Besides, it suppresses a core component of the intrinsic apoptotic pathway, granting tumor cells the ability to escape apoptosis induced by chemotherapeutic drugs. BMX knockout mouse have a normal lifespan, without an obvious altered phenotype, suggesting that therapies based on BMX inhibition, may have limited side effects. We developed a series of BMX-IN-1 analogues that showed an increased inhibitory capacity when compared to BMX-IN-1. Since crystallographic information is essential to understand the molecular basis of BMX inhibition by covalent inhibitors we establish a baculovirus-insect expression system protocol for the production of the recombinant human BMX. Here we report the full biochemical and biophysical characterization of human BMX alone and in complex with different covalent ligands.(...)" |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018 2018-09 2018-01-01T00:00:00Z 2021-09-30T00:30:25Z |
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://hdl.handle.net/10362/70422 |
url |
http://hdl.handle.net/10362/70422 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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 |
instname_str |
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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1799137972511047680 |