| http://purl.uniprot.org/citations/22219371 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22219371 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22219371 | http://www.w3.org/2000/01/rdf-schema#comment | "N-linked glycans play key roles in protein folding, stability, and function. Biosynthetic modification of N-linked glycans, within the endoplasmic reticulum, features sequential trimming and readornment steps. One unusual enzyme, endo-α-mannosidase, cleaves mannoside linkages internally within an N-linked glycan chain, short circuiting the classical N-glycan biosynthetic pathway. Here, using two bacterial orthologs, we present the first structural and mechanistic dissection of endo-α-mannosidase. Structures solved at resolutions 1.7-2.1 Å reveal a (β/α)(8) barrel fold in which the catalytic center is present in a long substrate-binding groove, consistent with cleavage within the N-glycan chain. Enzymatic cleavage of authentic Glc(1/3)Man(9)GlcNAc(2) yields Glc(1/3)-Man. Using the bespoke substrate α-Glc-1,3-α-Man fluoride, the enzyme was shown to act with retention of anomeric configuration. Complexes with the established endo-α-mannosidase inhibitor α-Glc-1,3-deoxymannonojirimycin and a newly developed inhibitor, α-Glc-1,3-isofagomine, and with the reducing-end product α-1,2-mannobiose structurally define the -2 to +2 subsites of the enzyme. These structural and mechanistic data provide a foundation upon which to develop new enzyme inhibitors targeting the hijacking of N-glycan synthesis in viral disease and cancer."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1111482109"xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1111482109"xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Davies G.J."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Davies G.J."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Gloster T.M."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Gloster T.M."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Thomas-Oates J.E."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Thomas-Oates J.E."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Williams S.J."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Williams S.J."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Thompson A.J."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Thompson A.J."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Williams R.J."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Williams R.J."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Wennekes T."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Wennekes T."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Wrodnigg T.M."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Wrodnigg T.M."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Alonzi D.S."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Alonzi D.S."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Butters T.D."xsd:string |
| http://purl.uniprot.org/citations/22219371 | http://purl.uniprot.org/core/author | "Butters T.D."xsd:string |