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8YRL

Crystal structure of Aspergillus fumigatus Galactofuranosylransferase (AfGfsA) in complex with UDP and galactofuranose

Summary for 8YRL
Entry DOI10.2210/pdb8yrl/pdb
DescriptorGlycosyltransferase family 31 protein, MANGANESE (II) ION, URIDINE-5'-DIPHOSPHATE, ... (6 entities in total)
Functional Keywordsgalactofuranosylransferase galactofuranose, transferase
Biological sourceAspergillus fumigatus CEA10
Total number of polymer chains2
Total formula weight114957.99
Authors
Okuno, A.,Oka, T.,Chihara, Y.,Hirata, R.,Kadooka, C.,Teramoto, T.,Hira, D.,Kakuta, Y. (deposition date: 2024-03-21, release date: 2024-10-30, Last modification date: 2024-11-20)
Primary citationOka, T.,Okuno, A.,Hira, D.,Teramoto, T.,Chihara, Y.,Hirata, R.,Kadooka, C.,Kakuta, Y.
Substrate binding and catalytic mechanism of UDP-alpha-D-galactofuranose: beta-galactofuranoside beta-(1→5)-galactofuranosyltransferase GfsA.
Pnas Nexus, 3:pgae482-pgae482, 2024
Cited by
PubMed Abstract: UDP-α-D-galactofuranose (UDP-Galf): β-galactofuranoside β-(1→5)-galactofuranosyltransferase, known as GfsA, is essential in synthesizing β-(1→5)-galactofuranosyl oligosaccharides that are incorporated into the cell wall of pathogenic fungi. This study analyzed the structure and function of GfsA from . To provide crucial insights into the catalytic mechanism and substrate recognition, the complex structure was elucidated with manganese (Mn), a donor substrate product (UDP), and an acceptor sugar molecule (β-galactofuranose). In addition to the typical GT-A fold domain, GfsA has a unique domain formed by the N and C termini. The former interacts with the GT-A of another GfsA, forming a dimer. The active center that contains Mn, UDP, and galactofuranose forms a groove structure that is highly conserved in the GfsA of Pezizomycotina fungi. Enzymatic assays using site-directed mutants were conducted to determine the roles of specific active-site residues in the enzymatic activity of GfsA. The predicted enzyme-substrate complex model containing UDP-Galf characterized a specific β-galactofuranosyltransfer mechanism to the 5'-OH of β-galactofuranose. Overall, the structure of GfsA in pathogenic fungi provides insights into the complex glycan biosynthetic processes of fungal pathogenesis and may inform the development of novel antifungal therapies.
PubMed: 39507050
DOI: 10.1093/pnasnexus/pgae482
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.37 Å)
Structure validation

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