7BOO
Crystal Structure of Core-mannan synthase A (CmsA/Ktr4) from Aspergillus fumigatus, apo form
Summary for 7BOO
| Entry DOI | 10.2210/pdb7boo/pdb |
| Descriptor | Alpha-1,2-mannosyltransferase (Ktr4), putative, SODIUM ION, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | mannosyltransferase, transferase |
| Biological source | Neosartorya fumigata (strain CEA10 / CBS 144.89 / FGSC A1163) |
| Total number of polymer chains | 6 |
| Total formula weight | 273903.13 |
| Authors | |
| Primary citation | Hira, D.,Onoue, T.,Oka, T. Structural basis for the core-mannan biosynthesis of cell wall fungal-type galactomannan in Aspergillus fumigatus . J.Biol.Chem., 295:15407-15417, 2020 Cited by PubMed Abstract: Fungal cell walls and their biosynthetic enzymes are potential targets for novel antifungal agents. Recently, two mannosyltransferases, namely core-mannan synthases A (CmsA/Ktr4) and B (CmsB/Ktr7), were found to play roles in the core-mannan biosynthesis of fungal-type galactomannan. CmsA/Ktr4 is an α-(1→2)-mannosyltransferase responsible for α-(1→2)-mannan biosynthesis in fungal-type galactomannan, which covers the cell surface of Strains with disrupted / have been shown to exhibit strongly suppressed hyphal elongation and conidiation alongside reduced virulence in a mouse model of invasive aspergillosis, indicating that CmsA/Ktr4 is a potential novel antifungal candidate. In this study we present the 3D structures of the soluble catalytic domain of CmsA/Ktr4, as determined by X-ray crystallography at a resolution of 1.95 Å, as well as the enzyme and Mn/GDP complex to 1.90 Å resolution. The CmsA/Ktr4 protein not only contains a highly conserved binding pocket for the donor substrate, GDP-mannose, but also has a unique broad cleft structure formed by its N- and C-terminal regions and is expected to recognize the acceptor substrate, a mannan chain. Based on these crystal structures, we also present a 3D structural model of the enzyme-substrate complex generated using docking and molecular dynamics simulations with α-Man-(1→6)-α-Man-(1→2)-α-Man-OMe as the model structure for the acceptor substrate. This predicted enzyme-substrate complex structure is also supported by findings from single amino acid substitution CmsA/Ktr4 mutants expressed in Δ cells. Taken together, these results provide basic information for developing specific α-mannan biosynthesis inhibitors for use as pharmaceuticals and/or pesticides. PubMed: 32873705DOI: 10.1074/jbc.RA120.013742 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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