Effect of Lipid Charge on Membrane Immersion of Cytochrome P450 3A4
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
27723344
DOI
10.1021/acs.jpcb.6b10108
Knihovny.cz E-zdroje
- MeSH
- cytochrom P-450 CYP3A chemie metabolismus MeSH
- králíci MeSH
- lidé MeSH
- lipidové dvojvrstvy chemie metabolismus MeSH
- lipidy chemie MeSH
- mikrozomy chemie metabolismus MeSH
- simulace molekulární dynamiky MeSH
- statická elektřina MeSH
- vodíková vazba MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CYP3A4 protein, human MeSH Prohlížeč
- cytochrom P-450 CYP3A MeSH
- lipidové dvojvrstvy MeSH
- lipidy MeSH
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.
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