Correction to: Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase (Nature Communications, (2023), 14, 1, (5785), 10.1038/s41467-023-41238-1)

Soluble HMW1C-like N-glycosyltransferases (NGTs) catalyze the glycosylation of Asn residues in proteins, a process fundamental for bacterial autoaggregation, adhesion and pathogenicity. However, our understanding of their molecular mechanisms is hindered by the lack of structures of enzymatic comple...

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Autores: Piniello, Beatriz, Macías-León, Javier, Miyazaki, Shun, García-García, Abel, Compañón, Ismael, Ghirardello, Mattia, Taleb, Víctor, Veloz, Billy, Corzana, Francisco, Miyagawa, Atsushi, Rovira i Virgili, Carme, Hurtado-Guerrero, Ramon
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/219742
Acceso en línea:https://hdl.handle.net/2445/219742
Access Level:acceso abierto
Palabra clave:Dinàmica molecular
Glúcids
Enzims
Molecular dynamics
Glucides
Enzymes
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spelling Correction to: Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase (Nature Communications, (2023), 14, 1, (5785), 10.1038/s41467-023-41238-1)Piniello, BeatrizMacías-León, JavierMiyazaki, ShunGarcía-García, AbelCompañón, IsmaelGhirardello, MattiaTaleb, VíctorVeloz, BillyCorzana, FranciscoMiyagawa, AtsushiRovira i Virgili, CarmeHurtado-Guerrero, RamonDinàmica molecularGlúcidsEnzimsMolecular dynamicsGlucidesEnzymesSoluble HMW1C-like N-glycosyltransferases (NGTs) catalyze the glycosylation of Asn residues in proteins, a process fundamental for bacterial autoaggregation, adhesion and pathogenicity. However, our understanding of their molecular mechanisms is hindered by the lack of structures of enzymatic complexes. Here, we report structures of binary and ternary NGT complexes of Aggregatibacter aphrophilus NGT (AaNGT), revealing an essential dyad of basic/acidic residues located in the N-terminal all α-domain (AAD) that intimately recognizes the Thr residue within the conserved motif Asn0-X+1-Ser/Thr+2. Poor substrates and inhibitors such as UDP-galactose and UDP-glucose mimetics adopt non-productive conformations, decreasing or impeding catalysis. QM/MM simulations rationalize these results, showing that AaNGT follows a SN2 reaction mechanism in which the acceptor asparagine uses its imidic form for catalysis and the UDP-glucose phosphate group acts as a general base. These findings provide key insights into the mechanism of NGTs and will facilitate the design of structure-based inhibitors to treat diseases caused by non-typeable H. influenzae or other Gram-negative bacteria.Nature Publishing Group2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/219742Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41467-023-41238-1Nature Communications, 2024, vol. 15, num.1https://doi.org/10.1038/s41467-023-41238-1cc-by (c) Piniello, B. et al., 2024http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2197422026-05-27T06:46:51Z
dc.title.none.fl_str_mv Correction to: Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase (Nature Communications, (2023), 14, 1, (5785), 10.1038/s41467-023-41238-1)
title Correction to: Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase (Nature Communications, (2023), 14, 1, (5785), 10.1038/s41467-023-41238-1)
spellingShingle Correction to: Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase (Nature Communications, (2023), 14, 1, (5785), 10.1038/s41467-023-41238-1)
Piniello, Beatriz
Dinàmica molecular
Glúcids
Enzims
Molecular dynamics
Glucides
Enzymes
title_short Correction to: Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase (Nature Communications, (2023), 14, 1, (5785), 10.1038/s41467-023-41238-1)
title_full Correction to: Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase (Nature Communications, (2023), 14, 1, (5785), 10.1038/s41467-023-41238-1)
title_fullStr Correction to: Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase (Nature Communications, (2023), 14, 1, (5785), 10.1038/s41467-023-41238-1)
title_full_unstemmed Correction to: Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase (Nature Communications, (2023), 14, 1, (5785), 10.1038/s41467-023-41238-1)
title_sort Correction to: Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase (Nature Communications, (2023), 14, 1, (5785), 10.1038/s41467-023-41238-1)
dc.creator.none.fl_str_mv Piniello, Beatriz
Macías-León, Javier
Miyazaki, Shun
García-García, Abel
Compañón, Ismael
Ghirardello, Mattia
Taleb, Víctor
Veloz, Billy
Corzana, Francisco
Miyagawa, Atsushi
Rovira i Virgili, Carme
Hurtado-Guerrero, Ramon
author Piniello, Beatriz
author_facet Piniello, Beatriz
Macías-León, Javier
Miyazaki, Shun
García-García, Abel
Compañón, Ismael
Ghirardello, Mattia
Taleb, Víctor
Veloz, Billy
Corzana, Francisco
Miyagawa, Atsushi
Rovira i Virgili, Carme
Hurtado-Guerrero, Ramon
author_role author
author2 Macías-León, Javier
Miyazaki, Shun
García-García, Abel
Compañón, Ismael
Ghirardello, Mattia
Taleb, Víctor
Veloz, Billy
Corzana, Francisco
Miyagawa, Atsushi
Rovira i Virgili, Carme
Hurtado-Guerrero, Ramon
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Dinàmica molecular
Glúcids
Enzims
Molecular dynamics
Glucides
Enzymes
topic Dinàmica molecular
Glúcids
Enzims
Molecular dynamics
Glucides
Enzymes
description Soluble HMW1C-like N-glycosyltransferases (NGTs) catalyze the glycosylation of Asn residues in proteins, a process fundamental for bacterial autoaggregation, adhesion and pathogenicity. However, our understanding of their molecular mechanisms is hindered by the lack of structures of enzymatic complexes. Here, we report structures of binary and ternary NGT complexes of Aggregatibacter aphrophilus NGT (AaNGT), revealing an essential dyad of basic/acidic residues located in the N-terminal all α-domain (AAD) that intimately recognizes the Thr residue within the conserved motif Asn0-X+1-Ser/Thr+2. Poor substrates and inhibitors such as UDP-galactose and UDP-glucose mimetics adopt non-productive conformations, decreasing or impeding catalysis. QM/MM simulations rationalize these results, showing that AaNGT follows a SN2 reaction mechanism in which the acceptor asparagine uses its imidic form for catalysis and the UDP-glucose phosphate group acts as a general base. These findings provide key insights into the mechanism of NGTs and will facilitate the design of structure-based inhibitors to treat diseases caused by non-typeable H. influenzae or other Gram-negative bacteria.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/219742
url https://hdl.handle.net/2445/219742
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41467-023-41238-1
Nature Communications, 2024, vol. 15, num.1
https://doi.org/10.1038/s41467-023-41238-1
dc.rights.none.fl_str_mv cc-by (c) Piniello, B. et al., 2024
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Piniello, B. et al., 2024
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Química Inorgànica i Orgànica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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