5OA6

Crystal structure of ScGas2 in complex with compound 12

5OA6 の概要

• エントリーDOI: 10.2210/pdb5oa6/pdb
• 分子名称: 1,3-beta-glucanosyltransferase GAS2, (2~{R},3~{S},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-[(2~{R},3~{R},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-[(2~{R},3~{R},4~{S},5~{R},6~{R})-2-(hydroxymethyl)-3,5-bis(oxidanyl)-6-[4-(3-quinolin-1-ium-1-ylpropyl)-1,2,3-triazol-1-yl]oxan-4-yl]oxy-3,5-bis(oxidanyl)oxan-4-yl]oxy-oxane-3,4,5-triol, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Saccharomyces cerevisiae S288c
• 細胞内の位置: Cell membrane ; Lipid-anchor, GPI-anchor : Q06135
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 63496.05

構造登録者

Delso, I.,Valero-Gonzalez, J.,Gomollon-Bel, F.,Castro-Lopez, J.,Fang, W.,Navratilova, I.,Van Aalten, D.,Tejero, T.,Merino, P.,Hurtado-Guerrero, R. (登録日: 2017-06-21, 公開日: 2018-05-02, 最終更新日: 2024-11-13)

主引用文献

Delso, I.,Valero-Gonzalez, J.,Gomollon-Bel, F.,Castro-Lopez, J.,Fang, W.,Navratilova, I.,van Aalten, D.M.F.,Tejero, T.,Merino, P.,Hurtado-Guerrero, R.
Inhibitors against Fungal Cell Wall Remodeling Enzymes.
ChemMedChem, 13:128-132, 2018

PubMed Abstract: Fungal β-1,3-glucan glucanosyltransferases are glucan-remodeling enzymes that play important roles in cell wall integrity, and are essential for the viability of pathogenic fungi and yeasts. As such, they are considered possible drug targets, although inhibitors of this class of enzymes have not yet been reported. Herein we report a multidisciplinary approach based on a structure-guided design using a highly conserved transglycosylase from Sacharomyces cerevisiae, that leads to carbohydrate derivatives with high affinity for Aspergillus fumigatus Gel4. We demonstrate by X-ray crystallography that the compounds bind in the active site of Gas2/Gel4 and interact with the catalytic machinery. The topological analysis of noncovalent interactions demonstrates that the combination of a triazole with positively charged aromatic moieties are important for optimal interactions with Gas2/Gel4 through unusual pyridinium cation-π and face-to-face π-π interactions. The lead compound is capable of inhibiting AfGel4 with an IC value of 42 μm.

PubMed: 29164827
DOI: 10.1002/cmdc.201700720

実験手法

X-RAY DIFFRACTION (1.94 Å)