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Fully Autonomous Characterization and Data Collection from Crystals of Biological Macromolecules
Published on: March 22, 2019
A high-resolution data set of fatty acid-binding protein structures. II. Crystallographic overview, ligand classes
Andreas Ehler1, Joerg Benz1, Markus G Rudolph1
1Therapeutic Modalities, Innovation Center Basel, F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland.
None:
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the ligands covers various series in which the carboxylate and aliphatic groups of the natural fatty-acid ligands have been replaced by other moieties.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.
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