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Role of MurT C-Terminal Domain in the Amidation of Staphylococcus aureus Peptidoglycan

Bibliographic Details
Main Author: Gonçalves, Barbara V.
Publication Date: 2019
Other Authors: Portela, Raquel, Lobo, Ricardo, Figueiredo, Teresa A., Grilo, Inês R., Ludovice, Ana Madalena, de Lencastre, Herminia, Dias, Jorge S., Sobral, Rita G.
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10362/100936
Summary: Fundacao para a Ciencia e a Tecnologia (FCT) through grants PTDC/FIS-NAN/ 0117/2014 and PTDC/BIA-MIC/31645/2017. project UID/Multi/04378/2019 (Unidade de Ciencias Biomoleculares Aplicadas-UCIBIO), funded by FCT/MCTES; project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular), funded by FEDER through COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI); national funds through FCT; by project ONEIDA (LISBOA-01-0145-FEDER-016417), cofunded by FEEI (Fundos Europeus Estruturais e de Investimento) from the Programa Operacional Regional Lisboa 2020; and by national funds from FCT. Funding was also provided by European Society of Clinical Microbiology and Infectious Diseases research grant 2015, awarded to R.G.S. B.V.G., T.A.F., and I.R.G. were supported by fellowships SFRH/BD/131623/2017 respectively. J.S.D. acknowledges the National NMR Network (PTNMR) and Infrastructure Project ROTEIRO/0031/2013-PINFRA/22161/2016 (cofinanced by FEDER through COMPETE 2020, POCI, PORL, and FCT through PIDDAC).
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spelling Role of MurT C-Terminal Domain in the Amidation of Staphylococcus aureus PeptidoglycanDUF1727MurT-GatDStaphylococcus aureusantibiotic resistancecell wallpeptidoglycan amidationFundacao para a Ciencia e a Tecnologia (FCT) through grants PTDC/FIS-NAN/ 0117/2014 and PTDC/BIA-MIC/31645/2017. project UID/Multi/04378/2019 (Unidade de Ciencias Biomoleculares Aplicadas-UCIBIO), funded by FCT/MCTES; project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular), funded by FEDER through COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI); national funds through FCT; by project ONEIDA (LISBOA-01-0145-FEDER-016417), cofunded by FEEI (Fundos Europeus Estruturais e de Investimento) from the Programa Operacional Regional Lisboa 2020; and by national funds from FCT. Funding was also provided by European Society of Clinical Microbiology and Infectious Diseases research grant 2015, awarded to R.G.S. B.V.G., T.A.F., and I.R.G. were supported by fellowships SFRH/BD/131623/2017 respectively. J.S.D. acknowledges the National NMR Network (PTNMR) and Infrastructure Project ROTEIRO/0031/2013-PINFRA/22161/2016 (cofinanced by FEDER through COMPETE 2020, POCI, PORL, and FCT through PIDDAC).Glutamate amidation, a secondary modification of the peptidoglycan, was first identified in Staphylococcus aureus. It is catalyzed by the protein products of the murT and gatD genes, which are conserved and colocalized in the genomes of most sequenced Gram-positive bacterial species. The MurT-GatD complex is required for cell viability, full resistance to β-lactam antibiotics, and resistance to human lysozyme and is recognized as an attractive target for new antimicrobials. Great effort has been invested in the study of this step, culminating recently in three independent reports addressing the structural elucidation of the MurT-GatD complex. In this work, we demonstrate through the use of nonstructural approaches the critical and multiple roles of the C-terminal domain of MurT, annotated as DUF1727, in the MurT-GatD enzymatic complex. This domain provides the physical link between the two enzymatic activities and is essential for the amidation reaction. Copurification of recombinant MurT and GatD proteins and bacterial two-hybrid assays support the observation that the MurT-GatD interaction occurs through this domain. Most importantly, we provide in vivo evidence of the effect of substitutions at specific residues in DUF1727 on cell wall peptidoglycan amidation and on the phenotypes of oxacillin resistance and bacterial growth.DCV - Departamento de Ciências da VidaUCIBIO - Applied Molecular Biosciences UnitInstituto de Tecnologia Química e Biológica António Xavier (ITQB)Molecular, Structural and Cellular Microbiology (MOSTMICRO)DQ - Departamento de QuímicaRUNGonçalves, Barbara V.Portela, RaquelLobo, RicardoFigueiredo, Teresa A.Grilo, Inês R.Ludovice, Ana Madalenade Lencastre, HerminiaDias, Jorge S.Sobral, Rita G.2020-07-15T22:58:14Z2019-102019-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/100936eng0095-1137PURE: 16525102https://doi.org/10.1128/AAC.00957-19info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-22T17:46:31Zoai:run.unl.pt:10362/100936Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:17:37.780253Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Role of MurT C-Terminal Domain in the Amidation of Staphylococcus aureus Peptidoglycan
title Role of MurT C-Terminal Domain in the Amidation of Staphylococcus aureus Peptidoglycan
spellingShingle Role of MurT C-Terminal Domain in the Amidation of Staphylococcus aureus Peptidoglycan
Gonçalves, Barbara V.
DUF1727
MurT-GatD
Staphylococcus aureus
antibiotic resistance
cell wall
peptidoglycan amidation
title_short Role of MurT C-Terminal Domain in the Amidation of Staphylococcus aureus Peptidoglycan
title_full Role of MurT C-Terminal Domain in the Amidation of Staphylococcus aureus Peptidoglycan
title_fullStr Role of MurT C-Terminal Domain in the Amidation of Staphylococcus aureus Peptidoglycan
title_full_unstemmed Role of MurT C-Terminal Domain in the Amidation of Staphylococcus aureus Peptidoglycan
title_sort Role of MurT C-Terminal Domain in the Amidation of Staphylococcus aureus Peptidoglycan
author Gonçalves, Barbara V.
author_facet Gonçalves, Barbara V.
Portela, Raquel
Lobo, Ricardo
Figueiredo, Teresa A.
Grilo, Inês R.
Ludovice, Ana Madalena
de Lencastre, Herminia
Dias, Jorge S.
Sobral, Rita G.
author_role author
author2 Portela, Raquel
Lobo, Ricardo
Figueiredo, Teresa A.
Grilo, Inês R.
Ludovice, Ana Madalena
de Lencastre, Herminia
Dias, Jorge S.
Sobral, Rita G.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv DCV - Departamento de Ciências da Vida
UCIBIO - Applied Molecular Biosciences Unit
Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
Molecular, Structural and Cellular Microbiology (MOSTMICRO)
DQ - Departamento de Química
RUN
dc.contributor.author.fl_str_mv Gonçalves, Barbara V.
Portela, Raquel
Lobo, Ricardo
Figueiredo, Teresa A.
Grilo, Inês R.
Ludovice, Ana Madalena
de Lencastre, Herminia
Dias, Jorge S.
Sobral, Rita G.
dc.subject.por.fl_str_mv DUF1727
MurT-GatD
Staphylococcus aureus
antibiotic resistance
cell wall
peptidoglycan amidation
topic DUF1727
MurT-GatD
Staphylococcus aureus
antibiotic resistance
cell wall
peptidoglycan amidation
description Fundacao para a Ciencia e a Tecnologia (FCT) through grants PTDC/FIS-NAN/ 0117/2014 and PTDC/BIA-MIC/31645/2017. project UID/Multi/04378/2019 (Unidade de Ciencias Biomoleculares Aplicadas-UCIBIO), funded by FCT/MCTES; project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular), funded by FEDER through COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI); national funds through FCT; by project ONEIDA (LISBOA-01-0145-FEDER-016417), cofunded by FEEI (Fundos Europeus Estruturais e de Investimento) from the Programa Operacional Regional Lisboa 2020; and by national funds from FCT. Funding was also provided by European Society of Clinical Microbiology and Infectious Diseases research grant 2015, awarded to R.G.S. B.V.G., T.A.F., and I.R.G. were supported by fellowships SFRH/BD/131623/2017 respectively. J.S.D. acknowledges the National NMR Network (PTNMR) and Infrastructure Project ROTEIRO/0031/2013-PINFRA/22161/2016 (cofinanced by FEDER through COMPETE 2020, POCI, PORL, and FCT through PIDDAC).
publishDate 2019
dc.date.none.fl_str_mv 2019-10
2019-10-01T00:00:00Z
2020-07-15T22:58:14Z
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/10362/100936
url http://hdl.handle.net/10362/100936
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0095-1137
PURE: 16525102
https://doi.org/10.1128/AAC.00957-19
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
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