Structural and mechanistic insights into the cleavage of clustered O-glycan patches-containing glycoproteins by mucinases of the human gut

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Autor(es): dc.contributorUniversity of Zaragoza-
Autor(es): dc.contributorUniversitat de Barcelona-
Autor(es): dc.contributorUniversity of Copenhagen-
Autor(es): dc.contributorCentro de Investigación en Síntesis Química-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorInstitució Catalana de Recerca i Estudis Avancats (ICREA)-
Autor(es): dc.contributorFundación ARAID-
Autor(es): dc.creatorTaleb, Víctor-
Autor(es): dc.creatorLiao, Qinghua-
Autor(es): dc.creatorNarimatsu, Yoshiki-
Autor(es): dc.creatorGarcía-García, Ana-
Autor(es): dc.creatorCompañón, Ismael-
Autor(es): dc.creatorBorges, Rafael Junqueira-
Autor(es): dc.creatorGonzález-Ramírez, Andrés Manuel-
Autor(es): dc.creatorCorzana, Francisco-
Autor(es): dc.creatorClausen, Henrik-
Autor(es): dc.creatorRovira, Carme-
Autor(es): dc.creatorHurtado-Guerrero, Ramon-
Data de aceite: dc.date.accessioned2025-08-21T17:04:42Z-
Data de disponibilização: dc.date.available2025-08-21T17:04:42Z-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2022-11-30-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1038/s41467-022-32021-9-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/240538-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/240538-
Descrição: dc.descriptionMucinases of human gut bacteria cleave peptide bonds in mucins strictly depending on the presence of neighboring O-glycans. The Akkermansia muciniphila AM0627 mucinase cleaves specifically in between contiguous (bis) O-glycans of defined truncated structures, suggesting that this enzyme may recognize clustered O-glycan patches. Here, we report the structure and molecular mechanism of AM0627 in complex with a glycopeptide containing a bis-T (Galβ1-3GalNAcα1-O-Ser/Thr) O-glycan, revealing that AM0627 recognizes both the sugar moieties and the peptide sequence. AM0627 exhibits preference for bis-T over bis-Tn (GalNAcα1-O-Ser/Thr) O-glycopeptide substrates, with the first GalNAc residue being essential for cleavage. AM0627 follows a mechanism relying on a nucleophilic water molecule and a catalytic base Glu residue. Structural comparison among mucinases identifies a conserved Tyr engaged in sugar-π interactions in both AM0627 and the Bacteroides thetaiotaomicron BT4244 mucinase as responsible for the common activity of these two mucinases with bis-T/Tn substrates. Our work illustrates how mucinases through tremendous flexibility adapt to the diversity in distribution and patterns of O-glycans on mucins.-
Descrição: dc.descriptionMinisterio de Economía y Competitividad-
Descrição: dc.descriptionInstitute of Biocomputation and Physics of Complex Systems University of Zaragoza, Mariano Esquillor s/n, Campus Rio Ebro, Edificio I+D-
Descrição: dc.descriptionDepartament de Química Inorgánica i Orgánica (Secció de Química Orgánica) and Institut de Química Teorica i Computacional (IQTCUB) Universitat de Barcelona-
Descrição: dc.descriptionCopenhagen Center for Glycomics Department of Cellular and Molecular Medicine University of Copenhagen-
Descrição: dc.descriptionDepartamento de Química Universidad de La Rioja Centro de Investigación en Síntesis Química-
Descrição: dc.descriptionDepartamento de Biofísica e Farmacologia Instituto de Biociências Universidade Estadual Paulista (UNESP)-
Descrição: dc.descriptionInstitució Catalana de Recerca i Estudis Avancats (ICREA)-
Descrição: dc.descriptionFundación ARAID-
Descrição: dc.descriptionDepartamento de Biofísica e Farmacologia Instituto de Biociências Universidade Estadual Paulista (UNESP)-
Descrição: dc.descriptionMinisterio de Economía y Competitividad: PID2020-118893GB-I00-
Idioma: dc.languageen-
Relação: dc.relationNature Communications-
???dc.source???: dc.sourceScopus-
Título: dc.titleStructural and mechanistic insights into the cleavage of clustered O-glycan patches-containing glycoproteins by mucinases of the human gut-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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