About: Heme-Coordinating Inhibitors of Neuronal Nitric Oxide Synthase. Iron-Thioether Coordination Is Stabilized by Hydrophobic Contacts without Increased Inhibitor Potency

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About: Heme-Coordinating Inhibitors of Neuronal Nitric Oxide Synthase. Iron-Thioether Coordination Is Stabilized by Hydrophobic Contacts without Increased Inhibitor Potency Goto Sponge NotDistinct Permalink

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	The heme-thioether ligand interaction often occurs between heme iron and native methionine ligands, but thioether-based heme-coordinating (type II) inhibitors are uncommon due to the difficulty in stabilizing the Fe-S bond. Here, a thioether-based inhibitor (3) of neuronal nitric oxide synthase (nNOS) was designed, and its binding was characterized by spectrophotometry and crystallography. A crystal structure of inhibitor 3 coordinated to heme iron was obtained, representing, to our knowledge, the first crystal structure of a thioether inhibitor complexed to any heme enzyme. A series of related potential inhibitors (4-8) also were evaluated. Compounds 4-8 were all found to be type I (non-heme-coordinating) inhibitors of ferric nNOS, but 4 and 6-8 were found to switch to type II upon heme reduction to the ferrous state, reflecting the higher affinity of thioethers for ferrous heme than for ferric heme. Contrary to what has been widely thought, thioether-heme ligation was found not to increase inhibitor The heme-thioether ligand interaction often occurs between heme iron and native methionine ligands, but thioether-based heme-coordinating (type II) inhibitors are uncommon due to the difficulty in stabilizing the Fe-S bond. Here, a thioether-based inhibitor (3) of neuronal nitric oxide synthase (nNOS) was designed, and its binding was characterized by spectrophotometry and crystallography. A crystal structure of inhibitor 3 coordinated to heme iron was obtained, representing, to our knowledge, the first crystal structure of a thioether inhibitor complexed to any heme enzyme. A series of related potential inhibitors (4-8) also were evaluated. Compounds 4-8 were all found to be type I (non-heme-coordinating) inhibitors of ferric nNOS, but 4 and 6-8 were found to switch to type II upon heme reduction to the ferrous state, reflecting the higher affinity of thioethers for ferrous heme than for ferric heme. Contrary to what has been widely thought, thioether-heme ligation was found not to increase inhibitor (en)
Title	Heme-Coordinating Inhibitors of Neuronal Nitric Oxide Synthase. Iron-Thioether Coordination Is Stabilized by Hydrophobic Contacts without Increased Inhibitor Potency Heme-Coordinating Inhibitors of Neuronal Nitric Oxide Synthase. Iron-Thioether Coordination Is Stabilized by Hydrophobic Contacts without Increased Inhibitor Potency (en)
skos:prefLabel	Heme-Coordinating Inhibitors of Neuronal Nitric Oxide Synthase. Iron-Thioether Coordination Is Stabilized by Hydrophobic Contacts without Increased Inhibitor Potency Heme-Coordinating Inhibitors of Neuronal Nitric Oxide Synthase. Iron-Thioether Coordination Is Stabilized by Hydrophobic Contacts without Increased Inhibitor Potency (en)
skos:notation	RIV/00064165:_____/10:7001!RIV11-MZ0-00064165
http://linked.open...avai/riv/aktivita	I P Z
http://linked.open...avai/riv/aktivity	I, P(1M0520), Z(MSM0021620806)
http://linked.open...iv/cisloPeriodika	2
http://linked.open...vai/riv/dodaniDat	2011
http://linked.open...aciTvurceVysledku	Martásek, Pavel
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Všeobecná fakultní nemocnice v Praze / (nerozlišená součást)
http://linked.open...dnocenehoVysledku	261369
http://linked.open...ai/riv/idVysledku	RIV/00064165:_____/10:7001
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	crystal-structure; cytochrome-c; microsomal cytochrome-p-450; selective inhibitors; escherichia-coli; l-thiocitrulline; ligand-binding; complexes; brain; site (en)
http://linked.open.../riv/klicoveSlovo	escherichia-coli complexes site crystal-structure cytochrome-c ligand-binding selective inhibitors brain l-thiocitrulline microsomal cytochrome-p-450
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[D9C93503EB53]
http://linked.open...i/riv/nazevZdroje	Journal of the american chemical society
http://linked.open...in/vavai/riv/obor	CE
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	8 (xsd:int)
http://linked.open...vavai/riv/projekt	Center for Applied Genomics
http://linked.open...UplatneniVysledku	2010
http://linked.open...v/svazekPeriodika	132
http://linked.open...iv/tvurceVysledku	Martásek, Pavel Li, HY Poulos, TL Roman, LJ Silverman, RB Doukov, T. Martell, J. D. Soltis, M.
http://linked.open...ain/vavai/riv/wos	000275084600059
http://linked.open...n/vavai/riv/zamer	Molekulární biologie a patologie buňky za normy a u vybraných klinicky závažných patologických procesů
issn	0002-7863
number of pages	9 (xsd:int)

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