8PE2

Crystal structure of Gel4 in complex with Nanobody 3

8PE2 の概要

• エントリーDOI: 10.2210/pdb8pe2/pdb
• 分子名称: 1,3-beta-glucanosyltransferase, Nanobody 3, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: transglycosylase, b-1, 3-glucan, nanobodies, fungal diseases, transferase
• 由来する生物種: Aspergillus fumigatus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64602.83

構造登録者

Macias-Leon, J.,Redrado-Hernandez, S.,Castro-Lopez, J.,Sanz, A.B.,Arias, M.,Farkas, V.,Vincke, C.,Muyldermans, S.,Pardo, J.,Arroyo, J.,Galvez, E.,Hurtado-Guerrero, R. (登録日: 2023-06-13, 公開日: 2024-06-19, 最終更新日: 2024-11-13)

主引用文献

Redrado-Hernandez, S.,Macias-Leon, J.,Castro-Lopez, J.,Belen Sanz, A.,Dolader, E.,Arias, M.,Gonzalez-Ramirez, A.M.,Sanchez-Navarro, D.,Petryk, Y.,Farkas, V.,Vincke, C.,Muyldermans, S.,Garcia-Barbazan, I.,Del Agua, C.,Zaragoza, O.,Arroyo, J.,Pardo, J.,Galvez, E.M.,Hurtado-Guerrero, R.
Broad Protection against Invasive Fungal Disease from a Nanobody Targeting the Active Site of Fungal beta-1,3-Glucanosyltransferases.
Angew.Chem.Int.Ed.Engl., 63:e202405823-e202405823, 2024

PubMed Abstract: Invasive fungal disease accounts for about 3.8 million deaths annually, an unacceptable rate that urgently prompts the discovery of new knowledge-driven treatments. We report the use of camelid single-domain nanobodies (Nbs) against fungal β-1,3-glucanosyltransferases (Gel) involved in β-1,3-glucan transglycosylation. Crystal structures of two Nbs with Gel4 from Aspergillus fumigatus revealed binding to a dissimilar CBM43 domain and a highly conserved catalytic domain across fungal species, respectively. Anti-Gel4 active site Nb3 showed significant antifungal efficacy in vitro and in vivo prophylactically and therapeutically against different A. fumigatus and Cryptococcus neoformans isolates, reducing the fungal burden and disease severity, thus significantly improving immunocompromised animal survival. Notably, C. deneoformans (serotype D) strains were more susceptible to Nb3 and genetic Gel deletion than C. neoformans (serotype A) strains, indicating a key role for β-1,3-glucan remodelling in C. deneoformans survival. These findings add new insight about the role of β-1,3-glucan in fungal biology and demonstrate the potential of nanobodies in targeting fungal enzymes to combat invasive fungal diseases.

PubMed: 38856634
DOI: 10.1002/anie.202405823

実験手法

X-RAY DIFFRACTION (2.05 Å)