9G53

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

This is a non-PDB format compatible entry.

Summary for 9G53

• Entry DOI: 10.2210/pdb9g53/pdb
• Descriptor: UDP-N-acetylglucosamine diphosphorylase, 2-acetamido-2-deoxy-1-O-phosphono-alpha-D-glucopyranose, (3~{S})-3-azanyl-3-thiophen-2-yl-propanoic acid, ... (8 entities in total)
• Functional Keywords: aspergillus, uap1, fragment, transferase
• Biological source: Aspergillus fumigatus; More
• Total number of polymer chains: 4
• Total formula weight: 216765.86

Authors

Yan, K. (deposition date: 2024-07-16, release date: 2025-07-30, Last modification date: 2026-01-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.96 Å)