Behavior of Human Cytochromes P450 on Lipid Membranes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F13%3A33145675" target="_blank" >RIV/61989592:15310/13:33145675 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/13:33145675

Výsledek na webu

<a href="http://pubs.acs.org/doi/abs/10.1021/jp4059559" target="_blank" >http://pubs.acs.org/doi/abs/10.1021/jp4059559</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/jp4059559" target="_blank" >10.1021/jp4059559</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Behavior of Human Cytochromes P450 on Lipid Membranes

Popis výsledku v původním jazyce

Human cytochromes P450 (CYPs) are membrane-anchored enzymes involved in biotransformation of many marketed drugs. We constructed atomic models of six human CYPs (CYP1A2, 2A6, 2C9, 2D6, 2E1, and 3A4) anchored to a lipid bilayer to investigate the positions and orientations of CYPs on a membrane. We equilibrated the models by molecular dynamics simulations on a 100+ ns time scale. Catalytic domains of all studied CYPs were found to be partially immersed in the lipid bilayer, whereas the N-terminal part and F'/G' loop are deeply immersed The proximal side of the enzyme faces the cytosol, whereas the distal side, where openings of substrate access and product release channels to the active site are primarily located, points toward the lipid bilayer. Accesschannels with openings in the vicinity of the B/C and FIG loops are typically positioned below the lipid head groups, whereas the solvent channel points toward the membrane water interface. We found that the access channel opening positi

Název v anglickém jazyce

Behavior of Human Cytochromes P450 on Lipid Membranes

Popis výsledku anglicky

Human cytochromes P450 (CYPs) are membrane-anchored enzymes involved in biotransformation of many marketed drugs. We constructed atomic models of six human CYPs (CYP1A2, 2A6, 2C9, 2D6, 2E1, and 3A4) anchored to a lipid bilayer to investigate the positions and orientations of CYPs on a membrane. We equilibrated the models by molecular dynamics simulations on a 100+ ns time scale. Catalytic domains of all studied CYPs were found to be partially immersed in the lipid bilayer, whereas the N-terminal part and F'/G' loop are deeply immersed The proximal side of the enzyme faces the cytosol, whereas the distal side, where openings of substrate access and product release channels to the active site are primarily located, points toward the lipid bilayer. Accesschannels with openings in the vicinity of the B/C and FIG loops are typically positioned below the lipid head groups, whereas the solvent channel points toward the membrane water interface. We found that the access channel opening positi

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

—

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2013

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Physical Chemistry B

ISSN

1520-6106

e-ISSN

—

Svazek periodika

117

Číslo periodika v rámci svazku

39

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

11556-11564

Kód UT WoS článku

000326301000016

EID výsledku v databázi Scopus

—