title: 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.
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.
authors: Department of Biochemistry, Queen's University, Kingston, ON K7L 3N6, Canada.
authors: Mona N
authors: MN
authors: Rahman
authors: Jason Z
authors: JZ
authors: Vlahakis
authors: Dragic
authors: D
authors: Vukomanovic
authors: Walter A
authors: WA
authors: Szarek
authors: Kanji
authors: K
authors: Nakatsu
authors: Zongchao
authors: Z
authors: Jia
mesh_terms: D018360:Crystallography, X-Ray; D004148:Dioxolanes / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions
chemical_list: C543612:(2R,4S)-2-(2-(4-chlorophenyl)ethyl)-2-((1H-imidazol-1-yl)methyl)-4(((5-trifluoromethylpyridin-2-yl)thio)methyl)-1,3-dioxolane; D004148:Dioxolanes; D004791:Enzyme Inhibitors; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1