The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F16%3A33161527" target="_blank" >RIV/61989592:15310/16:33161527 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15110/16:33161527
Result on the web
<a href="http://dmd.aspetjournals.org/content/44/4/576" target="_blank" >http://dmd.aspetjournals.org/content/44/4/576</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1124/dmd.115.068569" target="_blank" >10.1124/dmd.115.068569</a>
Alternative languages
Result language
angličtina
Original language name
The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function
Original language description
This symposium summary, sponsored by the ASPET, was held at Experimental Biology 2015 on March 29, 2015, in Boston, Massachusetts. The symposium focused on: 1) the interactions of cytochrome P450s (P450s) with their redox partners; and 2) the role of the lipid membrane in their orientation and stabilization. Two presentations discussed the interactions of P450s with NADPH-P450 reductase (CPR) and cytochrome b(5). First, solution nuclear magnetic resonance was used to compare the protein interactions that facilitated either the hydroxylase or lyase activities of CYP17A1. The lyase interaction was stimulated by the presence of b(5) and 17 alpha-hydroxypregnenolone, whereas the hydroxylase reaction was predominant in the absence of b(5). The role of b(5) was also shown in vivo by selective hepatic knockout of b(5) from mice expressing CYP3A4 and CYP2D6; the lack of b(5) caused a decrease in the clearance of several substrates. The role of the membrane on P450 orientation was examined using computational methods, showing that the proximal region of the P450 molecule faced the aqueous phase. The distal region, containing the substrate-access channel, was associated with the membrane. The interaction of NADPH-P450 reductase (CPR) with the membrane was also described, showing the ability of CPR to "helicopter" above the membrane. Finally, the endoplasmic reticulum (ER) was shown to be heterogeneous, having ordered membrane regions containing cholesterol and more disordered regions. Interestingly, two closely related P450s, CYP1A1 and CYP1A2, resided in different regions of the ER. The structural characteristics of their localization were examined. These studies emphasize the importance of P450 protein organization to their function.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CF - Physical chemistry and theoretical chemistry
OECD FORD branch
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Result continuities
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)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Drug Metabolism and Disposition
ISSN
0090-9556
e-ISSN
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Volume of the periodical
44
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
576-590
UT code for WoS article
000372880600014
EID of the result in the Scopus database
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