A high-resolution data set of fatty acid-binding protein structures. II. Crystallographic overview, ligand classes and binding pose

2025/07/18 by A. Ehler, J. Benz, M.G. Rudolph · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Computer Science · Medicine · #Computational Drug Discovery Methods #Inflammatory mediators and NSAID effects #Peroxisome Proliferator-Activated Receptors

paper · doi:10.1107/s2059798325005728

openalex publication_date 2025/07/18 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31

Abstract

Fatty acid-binding protein isoforms 4 and 5 are potential diabetes and atherosclerosis targets. During a drug-design program aiming at dual isoform-specific FABP4/5 inhibitors with little or no affinity for FABP3, a set of crystal structures with a median resolution of 1.2 Å was generated. The chemical space of the ligands covers various series in which the carboxylate and aliphatic groups of the natural fatty-acid ligands have been replaced by other moieties. A summary of binding modes of the chemical series is also given with respect to how isoform specificity was achieved. Additionally, several bromine-containing ligands were identified that allowed SAD phasing, yielding an independent experimental confirmation of their chemical composition.

Citations

• Phasercrystallographic software
• A high-resolution data set of fatty acid-binding protein structures. I. Dynamics of FABP4 and ligand binding
• Halogen bonding: the σ-hole
• A high quality, industrial data set for binding affinity prediction: performance comparison in different early drug discovery scenarios

Cited by

• Perspective on a large-scale ligand structure characterization

Discussions

• A set of 229 crystal structures of human and mouse FABPs are reported with a median resolution of 1.2 Å, 216 of which have a ligand bound. Many structures also have additional affinity data. #IsoformS [bsky, 0 points, 0 comments]