About: Binding of Quinidine Radically Increases the Stability and Decreases the Flexibility of the Cytochrome P450 2D6 Active Site

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About: Binding of Quinidine Radically Increases the Stability and Decreases the Flexibility of the Cytochrome P450 2D6 Active Site Goto Sponge NotDistinct Permalink

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
rdfs:seeAlso	http://www.sciencedirect.com/science/article/pii/S0162013412000542
Description	Human cytochrome P450 2D6 (CYP2D6) is an enzyme of the CYP superfamily responsible for biotransformation of about 20% of drugs of known metabolism containing a basic nitrogen and a planar aromatic ring. Here, we present a combined experimental and computational study on the compressibility and ?exibility of unliganded and quinidine-bound CYP2D6. Experimentally, high-pressure induced Soret band shifts of the enzyme were measured by UV/VIS spectroscopy, while 100 ns all atomic molecular dynamics (MD) simulations in explicit water were used in the computational analysis. We identi?ed sharp differences between ligand-free and quinidine-bound CYP2D6 forms in compressibility, ?exibility parameters and active site solvation. While the unliganded CYP2D6 is compressible, quinidine binding signi?cantly rigidi?es the CYP2D6 active site. In addition, MD simulations show that quinidine binding results in pronounced reductions in active site ?exibility and solvation. Human cytochrome P450 2D6 (CYP2D6) is an enzyme of the CYP superfamily responsible for biotransformation of about 20% of drugs of known metabolism containing a basic nitrogen and a planar aromatic ring. Here, we present a combined experimental and computational study on the compressibility and ?exibility of unliganded and quinidine-bound CYP2D6. Experimentally, high-pressure induced Soret band shifts of the enzyme were measured by UV/VIS spectroscopy, while 100 ns all atomic molecular dynamics (MD) simulations in explicit water were used in the computational analysis. We identi?ed sharp differences between ligand-free and quinidine-bound CYP2D6 forms in compressibility, ?exibility parameters and active site solvation. While the unliganded CYP2D6 is compressible, quinidine binding signi?cantly rigidi?es the CYP2D6 active site. In addition, MD simulations show that quinidine binding results in pronounced reductions in active site ?exibility and solvation. (en)
Title	Binding of Quinidine Radically Increases the Stability and Decreases the Flexibility of the Cytochrome P450 2D6 Active Site Binding of Quinidine Radically Increases the Stability and Decreases the Flexibility of the Cytochrome P450 2D6 Active Site (en)
skos:prefLabel	Binding of Quinidine Radically Increases the Stability and Decreases the Flexibility of the Cytochrome P450 2D6 Active Site Binding of Quinidine Radically Increases the Stability and Decreases the Flexibility of the Cytochrome P450 2D6 Active Site (en)
skos:notation	RIV/61989592:15310/12:33141136!RIV13-MSM-15310___
http://linked.open...avai/predkladatel	Přírodovědecká fakulta
http://linked.open...avai/riv/aktivita	P S
http://linked.open...avai/riv/aktivity	P(ED0030/01/01), P(ED2.1.00/03.0058), P(EE2.3.20.0017), P(GA303/09/1001), P(GD203/09/H046), S
http://linked.open...iv/cisloPeriodika	MAY
http://linked.open...vai/riv/dodaniDat	2013
http://linked.open...aciTvurceVysledku	Otyepka, Michal Hendrychová, Tereza Berka, Karel
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	Univerzita Palackého v Olomouci / Přírodovědecká fakulta
http://linked.open...dnocenehoVysledku	124964
http://linked.open...ai/riv/idVysledku	RIV/61989592:15310/12:33141136
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	High pressure; Cytochrome P450; Flexibility; Molecular Dynamics; Quinidine; CYP2D6 (en)
http://linked.open.../riv/klicoveSlovo	Molecular Dynamics Quinidine Cytochrome P450 Flexibility CYP2D6 High pressure
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[CED8A8787E7A]
http://linked.open...i/riv/nazevZdroje	Journal of Inorganic Biochemistry
http://linked.open...in/vavai/riv/obor	FR
http://linked.open...ichTvurcuVysledku	3 (xsd:int)
http://linked.open...cetTvurcuVysledku	7 (xsd:int)
http://linked.open...vavai/riv/projekt	Structural Determinants of Substrate Specificity of Human Cytochromes P450 Biomedicine for regional development and human resources Regional Centre of Advanced Technologies and Materials Research team development of the Regional Centre of Advanced Technologies and Materials Biochemistry on the crossroad from in silico to in vitro
http://linked.open...UplatneniVysledku	2012
http://linked.open...v/svazekPeriodika	110
http://linked.open...iv/tvurceVysledku	Otyepka, Michal Anzenbacher, Pavel Anzenbacherová, Eva Hendrychová, Tereza Lange, Reinhard Berka, Karel Mašek, Vlastimil
http://linked.open...ain/vavai/riv/wos	000304335700008
issn	0162-0134
number of pages	5 (xsd:int)
http://bibframe.org/vocab/doi	10.1016/j.jinorgbio.2012.02.010
http://localhost/t...ganizacniJednotka	15310
is http://linked.open...avai/riv/vysledek of	Binding of Quinidine Radically Increases the Stability and Decreases the Flexibility of the Cytochrome P450 2D6 Active Site

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