118017 20240319080953.0 doi 10.1038/s41467-022-29833-0 sideral 128701 ART-2022-128701 eng González-Ramírez, A.M. Universidad de Zaragoza (orcid)0000-0002-5838-0857 Structural basis for the synthesis of the core 1 structure by C1GalT1 2022 Access copy available to the general public Unrestricted C1GalT1 is an essential inverting glycosyltransferase responsible for synthesizing the core 1 structure, a common precursor for mucin-type O-glycans found in many glycoproteins. To date, the structure of C1GalT1 and the details of substrate recognition and catalysis remain unknown. Through biophysical and cellular studies, including X-ray crystallography of C1GalT1 complexed to a glycopeptide, we report that C1GalT1 is an obligate GT-A fold dimer that follows a SN2 mechanism. The binding of the glycopeptides to the enzyme is mainly driven by the GalNAc moiety while the peptide sequence provides optimal kinetic and binding parameters. Interestingly, to achieve glycosylation, C1GalT1 recognizes a high-energy conformation of the a-GalNAc-Thr linkage, negligibly populated in solution. By imposing this 3D-arrangement on that fragment, characteristic of a-GalNAc-Ser peptides, C1GalT1 ensures broad glycosylation of both acceptor substrates. These findings illustrate a structural and mechanistic blueprint to explain glycosylation of multiple acceptor substrates, extending the repertoire of mechanisms adopted by glycosyltransferases. © 2022, The Author(s). info:eu-repo/grantAgreement/ES/AEI/BFU2016-75633-P info:eu-repo/grantAgreement/ES/AEI/PID2019-105451GB-I00 info:eu-repo/grantAgreement/ES/AEI/RTI-2018-099592-B-C21 info:eu-repo/grantAgreement/ES/DGA/E34-R17 info:eu-repo/grantAgreement/ES/DGA/LMP58-18 info:eu-repo/grantAgreement/EC/FP7/283570/EU/Transnational access and enhancement of integrated Biological Structure determination at synchrotron X-ray radiation facilities/BIOSTRUCT-X info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 16.6 2022 MULTIDISCIPLINARY SCIENCES 6 / 73 = 0.082 2022 Q1 T1 5.116 2022 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2022 Q1 Physics and Astronomy (miscellaneous) 2022 Q1 Chemistry (miscellaneous) 2022 Q1 24.9 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Grosso, A.S. Yang, Z. Compañón, I. Coelho, H. Narimatsu, Y. Clausen, H. Marcelo, F. Corzana, F. Hurtado-Guerrero, R. (orcid)0000-0002-3122-9401 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 13 (2022), 2398 [15 pp.] Nature communications 2041-1723 3039848 http://zaguan.unizar.es/record/118017/files/texto_completo.pdf Versión publicada 1641660 http://zaguan.unizar.es/record/118017/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:118017 articulos driver 2024-03-18-13:14:39 ARTICLE