3HOK

X-ray Crystal Structure of Human Heme Oxygenase-1 with (2R, 4S)-2-[2-(4-Chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane: A Novel, Inducible Binding Mode

Summary for 3HOK

• Entry DOI: 10.2210/pdb3hok/pdb
• Related: 1N45 3CZY
• Descriptor: Heme oxygenase 1, PROTOPORPHYRIN IX CONTAINING FE, 2-({[(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl}sulfanyl)-5-(trifluoromethyl)pyridine, ... (4 entities in total)
• Functional Keywords: protein-inhibitor complex, alpha helices, endoplasmic reticulum, heme, iron, metal-binding, microsome, oxidoreductase, phosphoprotein, polymorphism
• Biological source: Homo sapiens (human)
• Cellular location: Microsome: P09601
• Total number of polymer chains: 2
• Total formula weight: 55514.14

Authors

Rahman, M.N.,Jia, Z. (deposition date: 2009-06-02, release date: 2009-07-28, Last modification date: 2023-09-06)

Primary citation

Rahman, M.N.,Vlahakis, J.Z.,Vukomanovic, D.,Szarek, W.A.,Nakatsu, K.,Jia, Z.
X-ray crystal structure of human heme oxygenase-1 with (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane: a novel, inducible binding mode.
J.Med.Chem., 52:4946-4950, 2009

PubMed Abstract: The crystal structure of human heme oxygenase-1 (HO-1) in complex with (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane (4) reveals a novel, inducible binding mode. Inhibitor 4 coordinates the heme iron, with its chlorophenyl group bound in a distal hydrophobic pocket, as seen in previous structures. However, accommodation of the 5-trifluoromethylpyridin-2-yl group requires a significant shift in the proximal helix, inducing the formation of a hydrophobic pocket. This is the first example of an induced binding pocket observed in HO-1.

PubMed: 19601578
DOI: 10.1021/jm900434f

Experimental method

X-RAY DIFFRACTION (2.19 Å)