000118803 001__ 118803
000118803 005__ 20240319081005.0
000118803 0247_ $$2doi$$a10.1038/s41467-022-32021-9
000118803 0248_ $$2sideral$$a130284
000118803 037__ $$aART-2022-130284
000118803 041__ $$aeng
000118803 100__ $$0(orcid)0000-0001-9224-5854$$aTaleb, Víctor$$uUniversidad de Zaragoza
000118803 245__ $$aStructural and mechanistic insights into the cleavage of clustered O-glycan patches-containing glycoproteins by mucinases of the human gut
000118803 260__ $$c2022
000118803 5060_ $$aAccess copy available to the general public$$fUnrestricted
000118803 5203_ $$aMucinases 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.
000118803 536__ $$9info:eu-repo/grantAgreement/ES/AEI/BFU2016-75633-P$$9info:eu-repo/grantAgreement/ES/AEI/MDM-2017-0767$$9info:eu-repo/grantAgreement/ES/AEI/PID2019-105451GB-I00$$9info:eu-repo/grantAgreement/ES/AEI/PID2020-118893GB-I00$$9info:eu-repo/grantAgreement/ES/AEI/RTI-2018-099592-B-C21$$9info:eu-repo/grantAgreement/EUR/COST-Action/CA18103-INNOGLY$$9info:eu-repo/grantAgreement/ES/DGA/E34-R17$$9info:eu-repo/grantAgreement/ES/DGA/LMP58-18$$9info:eu-repo/grantAgreement/EC/FP7/283570/EU/Transnational access and enhancement of integrated Biological Structure determination at synchrotron X-ray radiation facilities/BIOSTRUCT-X$$9info:eu-repo/grantAgreement/EC/H2020/814102/EU/Training interdisciplinary glycoscientists to get a molecular-level grip on glycocodes at the human mucosa–microbiota interface/SWEET CROSSTALK$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 814102-SWEET CROSSTALK$$9info:eu-repo/grantAgreement/EC/H2020/951231/EU/Activity-Based Profiling of Glycoprocessing Enzymes for Human Health and a Sustainable Society/CARBOCENTRE$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 951231-CARBOCENTRE$$9info:eu-repo/grantAgreement/EC/H2020/956544/EU/Directing the immune response through designed nanomaterials/DIRNANO$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 956544-DIRNANO
000118803 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000118803 590__ $$a16.6$$b2022
000118803 592__ $$a5.116$$b2022
000118803 591__ $$aMULTIDISCIPLINARY SCIENCES$$b6 / 73 = 0.082$$c2022$$dQ1$$eT1
000118803 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2022$$dQ1
000118803 593__ $$aPhysics and Astronomy (miscellaneous)$$c2022$$dQ1
000118803 593__ $$aChemistry (miscellaneous)$$c2022$$dQ1
000118803 594__ $$a24.9$$b2022
000118803 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000118803 700__ $$aLiao, Qinghua
000118803 700__ $$aNarimatsu, Yoshiki
000118803 700__ $$0(orcid)0000-0003-3791-2997$$aGarcía-García, Ana$$uUniversidad de Zaragoza
000118803 700__ $$aCompañón, Ismael
000118803 700__ $$aJunqueira Borges, Rafael
000118803 700__ $$0(orcid)0000-0002-5838-0857$$aGonzález-Ramírez, Andrés Manuel$$uUniversidad de Zaragoza
000118803 700__ $$aCorzana, Francisco
000118803 700__ $$aClausen, Henrik
000118803 700__ $$aRovira, Carme
000118803 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero, Ramon
000118803 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000118803 773__ $$g13 (2022), 4324 [15 pp.]$$tNature communications$$x2041-1723
000118803 8564_ $$s3602070$$uhttps://zaguan.unizar.es/record/118803/files/texto_completo.pdf$$yVersión publicada
000118803 8564_ $$s2401712$$uhttps://zaguan.unizar.es/record/118803/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000118803 909CO $$ooai:zaguan.unizar.es:118803$$particulos$$pdriver
000118803 951__ $$a2024-03-18-14:31:19
000118803 980__ $$aARTICLE