Structure, sequon recognition and mechanism of tryptophan C-mannosyltransferase
| العنوان: | Structure, sequon recognition and mechanism of tryptophan C-mannosyltransferase |
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| المؤلفون: | Joël S. Bloch, Alan John, Runyu Mao, Somnath Mukherjee, Jérémy Boilevin, Rossitza N. Irobalieva, Tamis Darbre, Nichollas E. Scott, Jean-Louis Reymond, Anthony A. Kossiakoff, Ethan D. Goddard-Borger, Kaspar P. Locher |
| المصدر: | Bloch, Joël S; John, Alan; Mao, Runyu; Mukherjee, Somnath; Boilevin, Jérémy; Irobalieva, Rossitza N; Darbre, Tamis; Scott, Nichollas E; Reymond, Jean-Louis; Kossiakoff, Anthony A; Goddard-Borger, Ethan D; Locher, Kaspar P (2023). Structure, sequon recognition and mechanism of tryptophan C-mannosyltransferase. Nature chemical biology, 19(5), pp. 575-584. Springer Nature 10.1038/s41589-022-01219-9 <http://dx.doi.org/10.1038/s41589-022-01219-9> Nature Chemical Biology, 19 (5) |
| بيانات النشر: | Springer Nature, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Enzyme mechanism, Glycobiology, Structural biology, 540 Chemie, 540 Chemistry, 570 Life sciences, biology, 610 Medicine & health, Cell Biology, 610 Medizin und Gesundheit, Molecular Biology, 570 Biowissenschaften, Biologie |
| الوصف: | C-linked glycosylation is essential for the trafficking, folding and function of secretory and transmembrane proteins involved in cellular communication processes. The tryptophan C-mannosyltransferase (CMT) enzymes that install the modification attach a mannose to the first tryptophan of WxxW/C sequons in nascent polypeptide chains by an unknown mechanism. Here, we report cryogenic-electron microscopy structures of Caenorhabditiselegans CMT in four key states: apo, acceptor peptide-bound, donor-substrate analog-bound and as a trapped ternary complex with both peptide and a donor-substrate mimic bound. The structures indicate how the C-mannosylation sequon is recognized by this CMT and its paralogs, and how sequon binding triggers conformational activation of the donor substrate: a process relevant to all glycosyltransferase C superfamily enzymes. Our structural data further indicate that the CMTs adopt an unprecedented electrophilic aromatic substitution mechanism to enable the C-glycosylation of proteins. These results afford opportunities for understanding human disease and therapeutic targeting of specific CMT paralogs. Nature Chemical Biology, 19 (5) ISSN:1552-4450 ISSN:1552-4469 |
| وصف الملف: | application/pdf; application/application/pdf |
| تدمد: | 1552-4450 1552-4469 |
| DOI: | 10.48350/176941 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3b3befc530922426b9dd0cdfdbc85a20 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3b3befc530922426b9dd0cdfdbc85a20 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15524450 15524469 |
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| DOI: | 10.48350/176941 |