Leonid Kaluzhskiy , Evgeniy Yablokov , Oksana Gnedenko , Dmitrii Burkatovskii , Ivan Maslov , Andrey Bogorodskiy , Pavel Ershov , Tatsiana Tsybruk , Elena Zelepuga , Tatyana Rutckova , Emma Kozlovskaya , Pavel Dmitrenok , Andrei Gilep , Valentin Borshchevskiy , Natallia Strushkevich , Alexis Ivanov
{"title":"The effect of membrane composition on the interaction between human CYP51 and its flavonoid inhibitor - luteolin 7,3′-disulfate","authors":"Leonid Kaluzhskiy , Evgeniy Yablokov , Oksana Gnedenko , Dmitrii Burkatovskii , Ivan Maslov , Andrey Bogorodskiy , Pavel Ershov , Tatsiana Tsybruk , Elena Zelepuga , Tatyana Rutckova , Emma Kozlovskaya , Pavel Dmitrenok , Andrei Gilep , Valentin Borshchevskiy , Natallia Strushkevich , Alexis Ivanov","doi":"10.1016/j.bbamem.2024.184286","DOIUrl":null,"url":null,"abstract":"<div><p><span>Cytochromes P450 (CYP) are a family of membrane proteins involved in the production of endogenous molecules and the metabolism of xenobiotics. It is well-known that the composition of the membrane can influence the activity and orientation of CYP proteins. However, little is known about how membrane composition affects the </span>ligand binding<span><span><span> properties of CYP. In this study, we utilized surface plasmon resonance and fluorescence lifetime analysis to examine the impact of membrane micro-environment composition on the interaction between human microsomal CYP51 (CYP51A1) and its inhibitor, </span>luteolin 7,3′-disulphate (LDS). We observed that membranes containing cholesterol or </span>sphingomyelin<span> exhibited the lowest apparent equilibrium dissociation constant<span> for the CYP51A1-LDS complex. Additionally, the tendency for relation between kinetic parameters of the CYP51A1-LDS complex and membrane viscosity and overall charge was observed. These findings suggest that the specific composition of the membrane, particularly the presence of cholesterol and sphingomyelin, plays a vital role in regulating the interaction between CYP enzymes and their ligands.</span></span></span></p></div>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0005273624000178","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
Abstract
Cytochromes P450 (CYP) are a family of membrane proteins involved in the production of endogenous molecules and the metabolism of xenobiotics. It is well-known that the composition of the membrane can influence the activity and orientation of CYP proteins. However, little is known about how membrane composition affects the ligand binding properties of CYP. In this study, we utilized surface plasmon resonance and fluorescence lifetime analysis to examine the impact of membrane micro-environment composition on the interaction between human microsomal CYP51 (CYP51A1) and its inhibitor, luteolin 7,3′-disulphate (LDS). We observed that membranes containing cholesterol or sphingomyelin exhibited the lowest apparent equilibrium dissociation constant for the CYP51A1-LDS complex. Additionally, the tendency for relation between kinetic parameters of the CYP51A1-LDS complex and membrane viscosity and overall charge was observed. These findings suggest that the specific composition of the membrane, particularly the presence of cholesterol and sphingomyelin, plays a vital role in regulating the interaction between CYP enzymes and their ligands.
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