3ZF8
Crystal structure of Saccharomyces cerevisiae Mnn9 in complex with GDP and Mn.
Summary for 3ZF8
| Entry DOI | 10.2210/pdb3zf8/pdb |
| Descriptor | MANNAN POLYMERASE COMPLEXES SUBUNIT MNN9, GUANOSINE-5'-DIPHOSPHATE, MANGANESE (II) ION, ... (4 entities in total) |
| Functional Keywords | transferase |
| Biological source | SACCHAROMYCES CEREVISIAE (BAKER'S YEAST) |
| Cellular location | Endoplasmic reticulum membrane; Single-pass type II membrane protein: P39107 |
| Total number of polymer chains | 1 |
| Total formula weight | 35538.76 |
| Authors | Striebeck, A.,Schuettelkopf, A.W.,van Aalten, D.M.F. (deposition date: 2012-12-10, release date: 2013-09-25, Last modification date: 2024-05-08) |
| Primary citation | Striebeck, A.,Robinson, D.A.,Schuettelkopf, A.W.,Van Aalten, D.M.F. Yeast Mnn9 is Both a Priming Glycosyltransferase and an Allosteric Activator of Mannan Biosynthesis. Open Biol., 3:30022-, 2013 Cited by PubMed Abstract: The fungal cell possesses an essential carbohydrate cell wall. The outer layer, mannan, is formed by mannoproteins carrying highly mannosylated O- and N-linked glycans. Yeast mannan biosynthesis is initiated by a Golgi-located complex (M-Pol I) of two GT-62 mannosyltransferases, Mnn9p and Van1p, that are conserved in fungal pathogens. Saccharomyces cerevisiae and Candida albicans mnn9 knockouts show an aberrant cell wall and increased antibiotic sensitivity, suggesting the enzyme is a potential drug target. Here, we present the structure of ScMnn9 in complex with GDP and Mn(2+), defining the fold and catalytic machinery of the GT-62 family. Compared with distantly related GT-78/GT-15 enzymes, ScMnn9 carries an unusual extension. Using a novel enzyme assay and site-directed mutagenesis, we identify conserved amino acids essential for ScMnn9 'priming' α-1,6-mannosyltransferase activity. Strikingly, both the presence of the ScMnn9 protein and its product, but not ScMnn9 catalytic activity, are required to activate subsequent ScVan1 processive α-1,6-mannosyltransferase activity in the M-Pol I complex. These results reveal the molecular basis of mannan synthesis and will aid development of inhibitors targeting this process. PubMed: 24026536DOI: 10.1098/RSOB.130022 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.98 Å) |
Structure validation
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