A water-bridged cysteine-cysteine redox regulation mechanism in bacterial protein tyrosine phosphatases
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2017 |
| Outros Autores: | , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/51576 |
Resumo: | © 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
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A water-bridged cysteine-cysteine redox regulation mechanism in bacterial protein tyrosine phosphatasesMycobacterium tuberculosisSDG3Good health and well-beingBiophysicsChemical biologyChemical mutagenesisComputational chemistryEnzymologyProtein tyrosine phosphataseWater bridge© 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).The emergence of multidrug-resistant Mycobacterium tuberculosis (Mtb) strains highlights the need to develop more efficacious and potent drugs. However, this goal is dependent on a comprehensive understanding of Mtb virulence protein effectors at the molecular level. Here, we used a post-expression cysteine (Cys)-to-dehydrolanine (Dha) chemical editing strategy to identify a water-mediated motif that modulates accessibility of the protein tyrosine phosphatase A (PtpA) catalytic pocket. Importantly, this water-mediated Cys-Cys non-covalent motif is also present in the phosphatase SptpA from Staphylococcus aureus, which suggests a potentially preserved structural feature among bacterial tyrosine phosphatases. The identification of this structural water provides insight into the known resistance of Mtb PtpA to the oxidative conditions that prevail within an infected host macrophage. This strategy could be applied to extend the understanding of the dynamics and function(s) of proteins in their native state and ultimately aid in the design of small-molecule modulators.We thank CNPq Brazil (fellowship 200456/2015-6 to J.B.B. and grants 454507/2014-3 and 300606/2010-9 to H.T.), the Fundação para a Ciência e a Tecnologia (FCT Investigator award IF/00624/2015 to G.J.L.B.), the European Union (Marie-Sklodowska Curie Innovative Training Network Protein Conjugates; Marie Skłodowska-Curie Individual Fellowship 743640 to T.R.; Marie-Curie Intra-European Fellowship 626890 to O.B.), the Ministerio de Economía, Industria, y Competitividad (project CTQ2015-67727-R to F.C.), and the Biotechnology and Biological Sciences Research Council (PhD studentship to L.D.) for funding. G.J.L.B. is a Royal Society University Research Fellow and the recipient of a European Research Council Starting Grant (TagIt, 676832). We also acknowledge funding by LISBOA-01-0145-FEDER-007391, co-financed by FEDER through the Programa Operacional Regional de Lisboa (Lisboa 2020) of PORTUGAL 2020 and by FCT Portugal.ElsevierRepositório da Universidade de LisboaBertoldo, Jean B.Rodrigues, TiagoDunsmore, LaviniaAprile, Francesco A.Marques, Marta C.Rosado, Leonardo A.Boutureira, OmarSteinbrecher, Thomas B.Sherman, WoodyCorzana, FranciscoTerenzi, HernánBernardes, Gonçalo J. L.2022-03-02T17:04:21Z20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/51576engChem. 2017 Oct 12;3(4):665-6772451-930810.1016/j.chempr.2017.07.0092451-9294info: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:RCAAP2023-11-08T16:56:22Zoai:repositorio.ul.pt:10451/51576Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:02:51.304940Repositório 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 |
A water-bridged cysteine-cysteine redox regulation mechanism in bacterial protein tyrosine phosphatases |
| title |
A water-bridged cysteine-cysteine redox regulation mechanism in bacterial protein tyrosine phosphatases |
| spellingShingle |
A water-bridged cysteine-cysteine redox regulation mechanism in bacterial protein tyrosine phosphatases Bertoldo, Jean B. Mycobacterium tuberculosis SDG3 Good health and well-being Biophysics Chemical biology Chemical mutagenesis Computational chemistry Enzymology Protein tyrosine phosphatase Water bridge |
| title_short |
A water-bridged cysteine-cysteine redox regulation mechanism in bacterial protein tyrosine phosphatases |
| title_full |
A water-bridged cysteine-cysteine redox regulation mechanism in bacterial protein tyrosine phosphatases |
| title_fullStr |
A water-bridged cysteine-cysteine redox regulation mechanism in bacterial protein tyrosine phosphatases |
| title_full_unstemmed |
A water-bridged cysteine-cysteine redox regulation mechanism in bacterial protein tyrosine phosphatases |
| title_sort |
A water-bridged cysteine-cysteine redox regulation mechanism in bacterial protein tyrosine phosphatases |
| author |
Bertoldo, Jean B. |
| author_facet |
Bertoldo, Jean B. Rodrigues, Tiago Dunsmore, Lavinia Aprile, Francesco A. Marques, Marta C. Rosado, Leonardo A. Boutureira, Omar Steinbrecher, Thomas B. Sherman, Woody Corzana, Francisco Terenzi, Hernán Bernardes, Gonçalo J. L. |
| author_role |
author |
| author2 |
Rodrigues, Tiago Dunsmore, Lavinia Aprile, Francesco A. Marques, Marta C. Rosado, Leonardo A. Boutureira, Omar Steinbrecher, Thomas B. Sherman, Woody Corzana, Francisco Terenzi, Hernán Bernardes, Gonçalo J. L. |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Bertoldo, Jean B. Rodrigues, Tiago Dunsmore, Lavinia Aprile, Francesco A. Marques, Marta C. Rosado, Leonardo A. Boutureira, Omar Steinbrecher, Thomas B. Sherman, Woody Corzana, Francisco Terenzi, Hernán Bernardes, Gonçalo J. L. |
| dc.subject.por.fl_str_mv |
Mycobacterium tuberculosis SDG3 Good health and well-being Biophysics Chemical biology Chemical mutagenesis Computational chemistry Enzymology Protein tyrosine phosphatase Water bridge |
| topic |
Mycobacterium tuberculosis SDG3 Good health and well-being Biophysics Chemical biology Chemical mutagenesis Computational chemistry Enzymology Protein tyrosine phosphatase Water bridge |
| description |
© 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| publishDate |
2017 |
| dc.date.none.fl_str_mv |
2017 2017-01-01T00:00:00Z 2022-03-02T17:04:21Z |
| 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 |
http://hdl.handle.net/10451/51576 |
| url |
http://hdl.handle.net/10451/51576 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Chem. 2017 Oct 12;3(4):665-677 2451-9308 10.1016/j.chempr.2017.07.009 2451-9294 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
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Elsevier |
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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 |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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