7FXN

Crystal Structure of human FABP4 in complex with 2-[(2S)-oxolan-2-yl]-4-phenyl-3-(1H-tetrazol-5-yl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine, i.e. SMILES c1(c(c(c2c(n1)CCCCC2)c1ccccc1)C1=NN=NN1)[C@@H]1CCCO1 with IC50=0.0357232 microM

Summary for 7FXN

• Entry DOI: 10.2210/pdb7fxn/pdb
• Group deposition: To be published (G_1002264)
• Descriptor: Fatty acid-binding protein, adipocyte, (3P)-2-[(2S)-oxolan-2-yl]-4-phenyl-3-(1H-tetrazol-5-yl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine, FORMIC ACID, ... (6 entities in total)
• Functional Keywords: lipid binding protein, fatty acid binding protein, cytoplasm, lipid-binding, transport, protein binding
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 15870.08

Authors

Ehler, A.,Benz, J.,Obst, U.,Obst-Sander, U.,Rudolph, M.G. (deposition date: 2023-04-27, release date: 2023-06-14, Last modification date: 2025-08-13)

Primary citation

Ehler, A.,Bartelmus, C.,Benz, J.,Plitzko, I.,Rudolph, M.G.
A high-resolution data set of fatty acid-binding protein structures. III. Unexpectedly high occurrence of wrong ligands.
Acta Crystallogr D Struct Biol, 81:451-464, 2025

PubMed Abstract: FABP4 has been implicated as a therapeutic target for treating diabetes and atherosclerosis. Structure-based drug design (SBDD) based on initial hits from high-throughput and fragment screens yielded 216 ligand-bound structures of human FABP3, FABP4 and FABP5 isoforms, many of which were at resolutions of better than 1.2 Å. An estimated 15% of the ligands had a different chemical composition to that expected from the starting materials or the final synthesis product, highlighting a potential problem inherent to all SBDD campaigns conducted at lower resolution. Apart from possible human error during compound registration, side reactions such as additions, eliminations, isomerizations, cyclizations and dimerizations were found that led to compounds capable of binding to FABP.

PubMed: 40748031
DOI: 10.1107/S2059798325006096

Experimental method

X-RAY DIFFRACTION (1.02 Å)