Effect of Lipid Charge on Membrane Immersion of Cytochrome P450 3A4

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F16%3A33160522" target="_blank" >RIV/61989592:15310/16:33160522 - isvavai.cz</a>

Výsledek na webu

<a href="http://pubs.acs.org/doi/full/10.1021/acs.jpcb.6b10108" target="_blank" >http://pubs.acs.org/doi/full/10.1021/acs.jpcb.6b10108</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jpcb.6b10108" target="_blank" >10.1021/acs.jpcb.6b10108</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Effect of Lipid Charge on Membrane Immersion of Cytochrome P450 3A4

Popis výsledku v původním jazyce

Microsomal cytochrome P450 enzymes (CYPs) are membrane-attached enzymes that play indispensable roles in biotransformations of numerous endogenous and exogenous compounds. Although recent progress in experiments and simulations has allowed many important features of CYP-membrane interactions to be deciphered, many other aspects remain underexplored. Using microsecond-long molecular dynamics simulations, we analyzed interaction of CYP3A4 with bilayers composed of lipids differing in their polar head groups, i.e., phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. In the negatively charged lipids, CYP3A4 was immersed more deeply and was more inclined toward the membrane because of favorable electrostatic and hydrogen bonding interactions between the CYP catalytic domain and lipid polar head groups. We showed that electrostatics significantly contributes to positioning and orientation of CYP on the membrane and might contribute to the experimentally observed preferences of individual CYP isoforms to distribute in (dis)ordered membrane microdomains.

Název v anglickém jazyce

Effect of Lipid Charge on Membrane Immersion of Cytochrome P450 3A4

Popis výsledku anglicky

Microsomal cytochrome P450 enzymes (CYPs) are membrane-attached enzymes that play indispensable roles in biotransformations of numerous endogenous and exogenous compounds. Although recent progress in experiments and simulations has allowed many important features of CYP-membrane interactions to be deciphered, many other aspects remain underexplored. Using microsecond-long molecular dynamics simulations, we analyzed interaction of CYP3A4 with bilayers composed of lipids differing in their polar head groups, i.e., phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. In the negatively charged lipids, CYP3A4 was immersed more deeply and was more inclined toward the membrane because of favorable electrostatic and hydrogen bonding interactions between the CYP catalytic domain and lipid polar head groups. We showed that electrostatics significantly contributes to positioning and orientation of CYP on the membrane and might contribute to the experimentally observed preferences of individual CYP isoforms to distribute in (dis)ordered membrane microdomains.

Druh

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

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

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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)

Rok uplatnění

2016

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

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Svazek periodika

120

Číslo periodika v rámci svazku

43

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

11205-11213

Kód UT WoS článku

000387198500013

EID výsledku v databázi Scopus

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