9G5F

The structure of Aspergillus fumigatus UDP-GlcNAc pyrophosphorylase in complex with a fragment

9G5F の概要

• エントリーDOI: 10.2210/pdb9g5f/pdb
• 分子名称: UDP-N-acetylglucosamine diphosphorylase, 2-acetamido-2-deoxy-1-O-phosphono-alpha-D-glucopyranose, 4-(2-hydroxyethyl)phenol, ... (6 entities in total)
• 機能のキーワード: aspergillus, uap1, fragment, transferase
• 由来する生物種: Aspergillus fumigatus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 216886.85

構造登録者

Yan, K. (登録日: 2024-07-16, 公開日: 2025-07-30, 最終更新日: 2026-01-28)

主引用文献

Yan, K.,Stanley, M.,Raimi, O.,Ferenbach, A.T.,Dorfmueller, H.C.,van Aalten, D.M.F.
Cell wall target fragment discovery using a low-cost, minimal fragment library.
Febs Lett., 2026

PubMed Abstract: Fragment-based inhibitor design is an established and widely used approach in drug discovery pipelines. Despite several examples of drugs originating from this approach, the identification of fragments still suffers from issues with solubility, reactivity, cost and worldwide accessibility. Here, we design a low-cost minimal fragment library (LoCoFrag100) for crystallographic screening, with an average cLogP of 0.03 (median 0.23) and an average of £20/g for each compound, facilitating assembly in any laboratory. Formatted in a 10 × 10 matrix to minimize Tanimoto similarity in the 20 cocktails, we demonstrate its applicability on three structurally distinct enzymes involved in microbial cell wall synthesis. Hit rates range from 1 to 6% among these enzymes, with three fragments suggesting avenues for inhibitor exploration. Impact Statement LoCoFrag100 is a low-cost, easily accessible fragment library that enables rapid survey of target ligandability in any laboratory, providing evidence to prioritise targets for follow-up research.

PubMed: 41532565
DOI: 10.1002/1873-3468.70281

実験手法

X-RAY DIFFRACTION (1.62 Å)