Related ArticlesInsights into the molecular basis of action of the AT1 antagonist losartan using a combined NMR spectroscopy and computational approach.
Biochim Biophys Acta. 2014 Mar;1838(3):1031-46
Authors: Zervou M, Cournia Z, Potamitis C, Patargias G, Durdagi S, Grdadolnik SG, Mavromoustakos T
Abstract
The drug:membrane interactions for the antihypertensive AT1 antagonist losartan, the prototype of the sartans class, are studied herein using an integrated approach. The pharmacophore arrangement of the drug was revealed by rotating frame nuclear Overhauser effect spectroscopy (2D ROESY) NMR spectroscopy in three different environments, namely water, dimethyl sulfoxide (DMSO), and sodium dodecyl sulfate (SDS) micellar solutions mimicking conditions of biological transport fluids and membrane lipid bilayers. Drug association with micelles was monitored by diffusion ordered spectroscopy (2D DOSY) and drug:micelle intermolecular interactions were characterized by ROESY spectroscopy. The localisation of the drug in the micellar environment was investigated by introducing 5-doxyl and 16-doxyl stearic acids. The use of spin labels confirmed that losartan resides close to the micelle:water interface with the hydroxymethyl group and the tetrazole heterocyclic aromatic ring facing the polar surface with the potential to interact with SDS charged polar head groups in order to increase amphiphilic interactions. The spontaneous insertion, the diffusion pathway and the conformational features of losartan were monitored by Molecular Dynamics (MD) simulations in a modeled SDS micellar aggregate environment and a long exploratory MD run (580ns) in a phospholipid dipalmitoylphosphatidylcholine (DPPC) bilayer with the AT1 receptor embedded. MD simulations were in excellent agreement with experimental results and further revealed the molecular basis of losartan:membrane interactions in atomic-level detail. This applied integrated approach aims to explore the role of membranes in losartan's pathway towards the AT1 receptor.
[NMR paper] Investigation of the mechanism of action of novel amphipathic peptides: Insights from solid-state NMR studies of oriented lipid bilayers.
Investigation of the mechanism of action of novel amphipathic peptides: Insights from solid-state NMR studies of oriented lipid bilayers.
Related Articles Investigation of the mechanism of action of novel amphipathic peptides: Insights from solid-state NMR studies of oriented lipid bilayers.
Biochim Biophys Acta. 2014 Feb 6;
Authors: Fillion M, Noël M, Lorin A, Voyer N, Auger M
Abstract
We have investigated in the present study the effect of both non-selective and selective cationic 14-mer peptides on the lipid orientation of DMPC bilayers...
[NMR paper] Structure and Topology of the Huntingtin 1-17 Membrane Anchor by*a*Combined Solution and Solid-State NMR Approach.
Structure and Topology of the Huntingtin 1-17 Membrane Anchor by*a*Combined Solution and Solid-State NMR Approach.
Structure and Topology of the Huntingtin 1-17 Membrane Anchor by*a*Combined Solution and Solid-State NMR Approach.
Biophys J. 2013 Aug 6;105(3):699-710
Authors: Michalek M, Salnikov ES, Bechinger B
Abstract
The very amino-terminal domain of the huntingtin protein is directly located upstream of the protein's polyglutamine tract, plays a decisive role in several important properties of this large protein and in the development...
nmrlearner
Journal club
0
08-13-2013 04:26 PM
[NMR paper] Molecular basis of the PED/PEA15 interaction with the C-terminal fragment of Phospholipase D1 revealed by NMR spectroscopy.
Molecular basis of the PED/PEA15 interaction with the C-terminal fragment of Phospholipase D1 revealed by NMR spectroscopy.
Related Articles Molecular basis of the PED/PEA15 interaction with the C-terminal fragment of Phospholipase D1 revealed by NMR spectroscopy.
Biochim Biophys Acta. 2013 Apr 19;
Authors: Farina B, Doti N, Pirone L, Malgieri G, Pedone EM, Ruvo M, Fattorusso R
Abstract
PED/PEA15 is a small protein involved in many protein-protein interactions that modulates the function of a number of key cellular effectors involved in...
[NMR paper] A new combined computational and NMR-spectroscopical strategy for the identification
A new combined computational and NMR-spectroscopical strategy for the identification of additional conformational constraints of the bound ligand in an aprotic solvent.
Related Articles A new combined computational and NMR-spectroscopical strategy for the identification of additional conformational constraints of the bound ligand in an aprotic solvent.
Chembiochem. 2000 Oct 2;1(3):181-95
Authors: Siebert HC, André S, Asensio JL, Cañada FJ, Dong X, Espinosa JF, Frank M, Gilleron M, Kaltner H, Kozár T, Bovin NV, von Der Lieth CW, Vliegenthart JF,...
nmrlearner
Journal club
0
11-19-2010 08:29 PM
Combined use of computational chemistry, NMR screening, and X-ray crystallography for
Combined use of computational chemistry, NMR screening, and X-ray crystallography for identification and characterization of fluorophilic protein environments.
Related Articles Combined use of computational chemistry, NMR screening, and X-ray crystallography for identification and characterization of fluorophilic protein environments.
Proteins. 2010 Jul 30;
Authors: Vulpetti A, Schiering N, Dalvit C
(19)F NMR screening of fluorinated fragments with different Local Environment of Fluorine, a.k.a. LEF library, is an experimental methodology...
nmrlearner
Journal club
0
10-05-2010 12:11 PM
Structural biology: Molecular machinery in action
News and Views
Nature 445, 609 (8 February 2007) | <abbr title="Digital Object Identifier">doi</abbr>:10.1038/nature05566; Published online 21 January 2007
Structural biology: Molecular machinery in action
Ad Bax and Dennis A. Torchia
Abstract
Insights into the molecular basis of action of the AT1 antagonist losartan using a combined NMR spectroscopy and computational approach.
Linear Mode
