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Nejvíce citované: 24417480

1 citací v PubMed Filtry

Nejvíce citovaný článek - PubMed ID 24417480

Amphiphilic drug-like molecules accumulate in a membrane below the head group region

The journal of physical chemistry. B. 2014 Jan 30 ; 118 (4) : 1030-9. [epub] 20140121

J Phys Chem B
ISSN 1520-5207
Zdroj

Článek

The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function

Scott, Emily E
Autor Scott, Emily E Departments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.)
Wolf, C Roland
Autor Wolf, C Roland Departments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.)
Otyepka, Michal
Autor Otyepka, Michal Departments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.)
Humphreys, Sara C
Autor Humphreys, Sara C Departments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.)
Reed, James R
Autor Reed, James R Departments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.)
Henderson, Colin J
Autor Henderson, Colin J Departments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.)
McLaughlin, Lesley A
Autor McLaughlin, Lesley A Departments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.)
Paloncýová, Markéta
Autor Paloncýová, Markéta Departments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.)
Navrátilová, Veronika
Autor Navrátilová, Veronika Departments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.)
Berka, Karel
Autor Berka, Karel Departments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.)

Drug metabolism and disposition: the biological fate of chemicals. 2016 Apr ; 44 (4) : 576-90. [epub] 20160205

Drug Metab Dispos
ISSN 1521-009X | 0090-9556
Zdroj

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 b5. 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 b5 and 17α-hydroxypregnenolone, whereas the hydroxylase reaction was predominant in the absence of b5. The role of b5 was also shown in vivo by selective hepatic knockout of b5 from mice expressing CYP3A4 and CYP2D6; the lack of b5 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.

MeSH
buněčná membrána metabolismus MeSH
endoplazmatické retikulum metabolismus MeSH
interakční proteinové domény a motivy fyziologie MeSH
jaterní mikrozomy metabolismus MeSH
lidé MeSH
sekundární struktura proteinů MeSH
systém (enzymů) cytochromů P-450 chemie fyziologie MeSH
výzkumná zpráva * MeSH
zvířata MeSH
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lidé MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
přehledy MeSH
Research Support, N.I.H., Extramural MeSH
Názvy látek
systém (enzymů) cytochromů P-450 MeSH

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Amphiphilic drug-like molecules accumulate in a membrane below the head group region

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