Author:
Carletta Andrea,Tilborg Anaëlle,Moineaux Laurence,de Ruyck Jérôme,Basile Livia,Salerno Loredana,Romeo Giuseppe,Wouters Johan,Guccione Salvatore
Abstract
Heme oxygenase-1 (HO-1) inhibition is associated with antitumor activity. Imidazole-based analogues show effective and selective inhibitory potency of HO-1. In this work, five single-crystal structures of four imidazole-based compounds are presented, with an in-depth structural analysis. In order to study the influence of the conformation of the ligands on binding to protein, conformational data from crystallography are compared with quantum mechanics analysis and molecular docking studies. Molecular docking of imidazole-based analogues in the active site of HO-1 is in good agreement with the experimental structures. Inhibitors interact with the heme cofactor and a hydrophobic pocket (Met34, Phe37, Val50, Leu147 and Phe214) in the HO-1 binding site. An alternate binding mode can be hypothesized for some inhibitors in the series.
Publisher
International Union of Crystallography (IUCr)
Subject
Materials Chemistry,Metals and Alloys,Atomic and Molecular Physics, and Optics,Electronic, Optical and Magnetic Materials
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