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

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F12%3A33141136" target="_blank" >RIV/61989592:15310/12:33141136 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15110/12:33141136
Result on the web
<a href="http://www.sciencedirect.com/science/article/pii/S0162013412000542" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0162013412000542</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jinorgbio.2012.02.010" target="_blank" >10.1016/j.jinorgbio.2012.02.010</a>

Result language
angličtina
Original language name
Binding of Quinidine Radically Increases the Stability and Decreases the Flexibility of the Cytochrome P450 2D6 Active Site
Original language 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.
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FR - Pharmacology and apothecary chemistry
OECD FORD branch
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Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Publication year
2012
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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