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- Title
How does binding of imidazole-based inhibitors to heme oxygenase-1 influence their conformation? Insights combining crystal structures and molecular modelling.
- Authors
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.
- Subjects
HEME oxygenase; IMIDAZOLES; MOLECULAR docking; MOLECULAR conformation; ANTINEOPLASTIC agents; CRYSTAL structure
- Publication
Acta Crystallographica Section B: Structural Science, Crystal Engineering & Materials, 2015, Vol 71, Issue 4, p447
- ISSN
2052-5192
- Publication type
Article
- DOI
10.1107/S2052520615010410