8YRL

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

8YRL の概要

• エントリーDOI: 10.2210/pdb8yrl/pdb
• 分子名称: Glycosyltransferase family 31 protein, MANGANESE (II) ION, URIDINE-5'-DIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: galactofuranosylransferase galactofuranose, transferase
• 由来する生物種: Aspergillus fumigatus CEA10
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 114957.99

構造登録者

Okuno, A.,Oka, T.,Chihara, Y.,Hirata, R.,Kadooka, C.,Teramoto, T.,Hira, D.,Kakuta, Y. (登録日: 2024-03-21, 公開日: 2024-10-30, 最終更新日: 2024-11-20)

主引用文献

Oka, 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

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

実験手法

X-RAY DIFFRACTION (2.37 Å)