TY - JOUR
T1 - The effect of membrane composition on the interaction between human CYP51 and its flavonoid inhibitor - luteolin 7,3′-disulfate
AU - Kaluzhskiy, Leonid
AU - Yablokov, Evgeniy
AU - Gnedenko, Oksana
AU - Burkatovskii, Dmitrii
AU - Maslov, Ivan
AU - Bogorodskiy, Andrey
AU - Ershov, Pavel
AU - Tsybruk, Tatsiana
AU - Zelepuga, Elena
AU - Rutckova, Tatyana
AU - Kozlovskaya, Emma
AU - Dmitrenok, Pavel
AU - Gilep, Andrei
AU - Borshchevskiy, Valentin
AU - Strushkevich, Natallia
AU - Ivanov, Alexis
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/3
Y1 - 2024/3
N2 - 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.
AB - 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.
KW - Flavonoids
KW - Fluorescence lifetime
KW - Kinetic-affinity relationships
KW - Lanosterol 14-alpha demethylase
KW - Model membrane
KW - Surface plasmon resonance
UR - http://www.scopus.com/inward/record.url?scp=85183994329&partnerID=8YFLogxK
U2 - 10.1016/j.bbamem.2024.184286
DO - 10.1016/j.bbamem.2024.184286
M3 - Article
C2 - 38272204
AN - SCOPUS:85183994329
SN - 0005-2736
VL - 1866
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 3
M1 - 184286
ER -