Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases

Detalhes bibliográficos
Autor(a) principal: Ruidan Shen
Data de Publicação: 2022
Outros Autores: Rory M. Crean, Keith J. Olsen, Marina Corbella Morató, Ana Rita Calixto, Teisha Richan, Tiago Antônio da Silva Brandão, Ryan D. Berry, Alex Tolman, Patrick Loria, Sean Johnson, Shina Caroline Lynn Kamerlin, Alvan C. Hengge
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFMG
Texto Completo: https://doi.org/10.1039/D2SC04135A
http://hdl.handle.net/1843/59751
https://orcid.org/0000-0003-2670-1035
https://orcid.org/0000-0003-4709-5353
https://orcid.org/0000-0002-2248-9789
https://orcid.org/0000-0001-9209-868X
https://orcid.org/0000-0002-1123-0413
https://orcid.org/0000-0001-5528-2293
https://orcid.org/0000-0002-7783-3014
https://orcid.org/0000-0002-0941-3560
https://orcid.org/0000-0001-7992-2494
https://orcid.org/0000-0002-3190-1173
https://orcid.org/0000-0002-5696-2087
Resumo: Outra Agência
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spelling 2023-10-19T19:44:47Z2023-10-19T19:44:47Z202213451352413540https://doi.org/10.1039/D2SC04135A2041-6539http://hdl.handle.net/1843/59751https://orcid.org/0000-0003-2670-1035https://orcid.org/0000-0003-4709-5353https://orcid.org/0000-0002-2248-9789https://orcid.org/0000-0001-9209-868Xhttps://orcid.org/0000-0002-1123-0413https://orcid.org/0000-0001-5528-2293https://orcid.org/0000-0002-7783-3014https://orcid.org/0000-0002-0941-3560https://orcid.org/0000-0001-7992-2494https://orcid.org/0000-0002-3190-1173https://orcid.org/0000-0002-5696-2087Outra AgênciaProtein tyrosine phosphatases (PTPs) possess a conserved mobile catalytic loop, the WPD-loop, which brings an aspartic acid into the active site where it acts as an acid/base catalyst. Prior experimental and computational studies, focused on the human enzyme PTP1B and the PTP from Yersinia pestis, YopH, suggested that loop conformational dynamics are important in regulating both catalysis and evolvability. We have generated a chimeric protein in which the WPD-loop of YopH is transposed into PTP1B, and eight chimeras that systematically restored the loop sequence back to native PTP1B. Of these, four chimeras were soluble and were subjected to detailed biochemical and structural characterization, and a computational analysis of their WPD-loop dynamics. The chimeras maintain backbone structural integrity, with somewhat slower rates than either wild-type parent, and show differences in the pH dependency of catalysis, and changes in the effect of Mg2+. The chimeric proteins' WPD-loops differ significantly in their relative stability and rigidity. The time required for interconversion, coupled with electrostatic effects revealed by simulations, likely accounts for the activity differences between chimeras, and relative to the native enzymes. Our results further the understanding of connections between enzyme activity and the dynamics of catalytically important groups, particularly the effects of non-catalytic residues on key conformational equilibria.engUniversidade Federal de Minas GeraisUFMGBrasilICX - DEPARTAMENTO DE QUÍMICAChemical ScienceProteinas - AnáliseAnálise enzimáticaAnálise conformacionalDinâmica molecularCinética de enzimasBioquímicaProtein tyrosine phosphatases (PTPs)Chimeric proteinConformational equilibriaMolecular dynamics (MD)Kinetic isotope effects (KIEs)Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatasesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://pubs.rsc.org/en/content/articlelanding/2022/SC/D2SC04135ARuidan ShenRory M. CreanKeith J. OlsenMarina Corbella MoratóAna Rita CalixtoTeisha RichanTiago Antônio da Silva BrandãoRyan D. BerryAlex TolmanPatrick LoriaSean JohnsonShina Caroline Lynn KamerlinAlvan C. Henggeapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALInsights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases.pdfInsights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases.pdfapplication/pdf13900351https://repositorio.ufmg.br/bitstream/1843/59751/2/Insights%20into%20the%20importance%20of%20WPD-loop%20sequence%20for%20activity%20and%20structure%20in%20protein%20tyrosine%20phosphatases.pdfffc0f563824c2294e872e4e3be92b159MD52LICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/59751/1/License.txtfa505098d172de0bc8864fc1287ffe22MD511843/597512023-10-19 16:44:47.689oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-10-19T19:44:47Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.pt_BR.fl_str_mv Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases
title Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases
spellingShingle Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases
Ruidan Shen
Protein tyrosine phosphatases (PTPs)
Chimeric protein
Conformational equilibria
Molecular dynamics (MD)
Kinetic isotope effects (KIEs)
Proteinas - Análise
Análise enzimática
Análise conformacional
Dinâmica molecular
Cinética de enzimas
Bioquímica
title_short Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases
title_full Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases
title_fullStr Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases
title_full_unstemmed Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases
title_sort Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases
author Ruidan Shen
author_facet Ruidan Shen
Rory M. Crean
Keith J. Olsen
Marina Corbella Morató
Ana Rita Calixto
Teisha Richan
Tiago Antônio da Silva Brandão
Ryan D. Berry
Alex Tolman
Patrick Loria
Sean Johnson
Shina Caroline Lynn Kamerlin
Alvan C. Hengge
author_role author
author2 Rory M. Crean
Keith J. Olsen
Marina Corbella Morató
Ana Rita Calixto
Teisha Richan
Tiago Antônio da Silva Brandão
Ryan D. Berry
Alex Tolman
Patrick Loria
Sean Johnson
Shina Caroline Lynn Kamerlin
Alvan C. Hengge
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Ruidan Shen
Rory M. Crean
Keith J. Olsen
Marina Corbella Morató
Ana Rita Calixto
Teisha Richan
Tiago Antônio da Silva Brandão
Ryan D. Berry
Alex Tolman
Patrick Loria
Sean Johnson
Shina Caroline Lynn Kamerlin
Alvan C. Hengge
dc.subject.por.fl_str_mv Protein tyrosine phosphatases (PTPs)
Chimeric protein
Conformational equilibria
Molecular dynamics (MD)
Kinetic isotope effects (KIEs)
topic Protein tyrosine phosphatases (PTPs)
Chimeric protein
Conformational equilibria
Molecular dynamics (MD)
Kinetic isotope effects (KIEs)
Proteinas - Análise
Análise enzimática
Análise conformacional
Dinâmica molecular
Cinética de enzimas
Bioquímica
dc.subject.other.pt_BR.fl_str_mv Proteinas - Análise
Análise enzimática
Análise conformacional
Dinâmica molecular
Cinética de enzimas
Bioquímica
description Outra Agência
publishDate 2022
dc.date.issued.fl_str_mv 2022
dc.date.accessioned.fl_str_mv 2023-10-19T19:44:47Z
dc.date.available.fl_str_mv 2023-10-19T19:44:47Z
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/1843/59751
dc.identifier.doi.pt_BR.fl_str_mv https://doi.org/10.1039/D2SC04135A
dc.identifier.issn.pt_BR.fl_str_mv 2041-6539
dc.identifier.orcid.pt_BR.fl_str_mv https://orcid.org/0000-0003-2670-1035
https://orcid.org/0000-0003-4709-5353
https://orcid.org/0000-0002-2248-9789
https://orcid.org/0000-0001-9209-868X
https://orcid.org/0000-0002-1123-0413
https://orcid.org/0000-0001-5528-2293
https://orcid.org/0000-0002-7783-3014
https://orcid.org/0000-0002-0941-3560
https://orcid.org/0000-0001-7992-2494
https://orcid.org/0000-0002-3190-1173
https://orcid.org/0000-0002-5696-2087
url https://doi.org/10.1039/D2SC04135A
http://hdl.handle.net/1843/59751
https://orcid.org/0000-0003-2670-1035
https://orcid.org/0000-0003-4709-5353
https://orcid.org/0000-0002-2248-9789
https://orcid.org/0000-0001-9209-868X
https://orcid.org/0000-0002-1123-0413
https://orcid.org/0000-0001-5528-2293
https://orcid.org/0000-0002-7783-3014
https://orcid.org/0000-0002-0941-3560
https://orcid.org/0000-0001-7992-2494
https://orcid.org/0000-0002-3190-1173
https://orcid.org/0000-0002-5696-2087
identifier_str_mv 2041-6539
dc.language.iso.fl_str_mv eng
language eng
dc.relation.ispartof.pt_BR.fl_str_mv Chemical Science
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.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
dc.publisher.initials.fl_str_mv UFMG
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv ICX - DEPARTAMENTO DE QUÍMICA
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
instname:Universidade Federal de Minas Gerais (UFMG)
instacron:UFMG
instname_str Universidade Federal de Minas Gerais (UFMG)
instacron_str UFMG
institution UFMG
reponame_str Repositório Institucional da UFMG
collection Repositório Institucional da UFMG
bitstream.url.fl_str_mv https://repositorio.ufmg.br/bitstream/1843/59751/2/Insights%20into%20the%20importance%20of%20WPD-loop%20sequence%20for%20activity%20and%20structure%20in%20protein%20tyrosine%20phosphatases.pdf
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