BioNMR
NMR aggregator & online community since 2003
BioNMR    
Learn or help to learn NMR - get free NMR books!
 

Go Back   BioNMR > Educational resources > Journal club
Advanced Search



Jobs Groups Conferences Literature Pulse sequences Software forums Programs Sample preps Web resources BioNMR issues


Webservers
NMR processing:
MDD
NMR assignment:
Backbone:
Autoassign
MARS
UNIO Match
PINE
Side-chains:
UNIO ATNOS-Ascan
NOEs:
UNIO ATNOS-Candid
UNIO Candid
ASDP
Structure from NMR restraints:
Ab initio:
GeNMR
Cyana
XPLOR-NIH
ASDP
UNIO ATNOS-Candid
UNIO Candid
Fragment-based:
BMRB CS-Rosetta
Rosetta-NMR (Robetta)
Template-based:
GeNMR
I-TASSER
Refinement:
Amber
Structure from chemical shifts:
Fragment-based:
WeNMR CS-Rosetta
BMRB CS-Rosetta
Homology-based:
CS23D
Simshift
Torsion angles from chemical shifts:
Preditor
TALOS
Promega- Proline
Secondary structure from chemical shifts:
CSI (via RCI server)
TALOS
MICS caps, β-turns
d2D
PECAN
Flexibility from chemical shifts:
RCI
Interactions from chemical shifts:
HADDOCK
Chemical shifts re-referencing:
Shiftcor
UNIO Shiftinspector
LACS
CheckShift
RefDB
NMR model quality:
NOEs, other restraints:
PROSESS
PSVS
RPF scores
iCing
Chemical shifts:
PROSESS
CheShift2
Vasco
iCing
RDCs:
DC
Anisofit
Pseudocontact shifts:
Anisofit
Protein geomtery:
Resolution-by-Proxy
PROSESS
What-If
iCing
PSVS
MolProbity
SAVES2 or SAVES4
Vadar
Prosa
ProQ
MetaMQAPII
PSQS
Eval123D
STAN
Ramachandran Plot
Rampage
ERRAT
Verify_3D
Harmony
Quality Control Check
NMR spectrum prediction:
FANDAS
MestReS
V-NMR
Flexibility from structure:
Backbone S2
Methyl S2
B-factor
Molecular dynamics:
Gromacs
Amber
Antechamber
Chemical shifts prediction:
From structure:
Shiftx2
Sparta+
Camshift
CH3shift- Methyl
ArShift- Aromatic
ShiftS
Proshift
PPM
CheShift-2- Cα
From sequence:
Shifty
Camcoil
Poulsen_rc_CS
Disordered proteins:
MAXOCC
Format conversion & validation:
CCPN
From NMR-STAR 3.1
Validate NMR-STAR 3.1
NMR sample preparation:
Protein disorder:
DisMeta
Protein solubility:
camLILA
ccSOL
Camfold
camGroEL
Zyggregator
Isotope labeling:
UPLABEL
Solid-state NMR:
sedNMR


Reply
Thread Tools Search this Thread Rate Thread Display Modes
  #1  
Unread 03-09-2011, 02:20 PM
nmrlearner's Avatar
Senior Member
 
Join Date: Jan 2005
Posts: 23,135
Points: 193,617, Level: 100
Points: 193,617, Level: 100 Points: 193,617, Level: 100 Points: 193,617, Level: 100
Level up: 0%, 0 Points needed
Level up: 0% Level up: 0% Level up: 0%
Activity: 50.7%
Activity: 50.7% Activity: 50.7% Activity: 50.7%
Last Achievements
Award-Showcase
NMR Credits: 0
NMR Points: 193,617
Downloads: 0
Uploads: 0
Default Specific Binding of Adamantane Drugs and Direction of Their Polar Amines in the Pore of the Influenza M2 Transmembrane Domain in Lipid Bilayers and Dodecylphosphocholine Micelles Determined by NMR Spectroscopy.

Specific Binding of Adamantane Drugs and Direction of Their Polar Amines in the Pore of the Influenza M2 Transmembrane Domain in Lipid Bilayers and Dodecylphosphocholine Micelles Determined by NMR Spectroscopy.

Specific Binding of Adamantane Drugs and Direction of Their Polar Amines in the Pore of the Influenza M2 Transmembrane Domain in Lipid Bilayers and Dodecylphosphocholine Micelles Determined by NMR Spectroscopy.

J Am Chem Soc. 2011 Mar 7;

Authors: Cady SD, Wang J, Wu Y, Degrado WF, Hong M

The transmembrane domain of the influenza M2 protein (M2TM) forms a tetrameric proton channel important for the virus lifecycle. The proton-channel activity is inhibited by amine-containing adamantyl drugs amantadine and rimantadine, which have been shown to bind specifically to the pore of M2TM near Ser31. However, whether the polar amine points to the N- or C-terminus of the channel has not yet been determined. Elucidating the polar group direction will shed light on the mechanism by which drug binding inhibits this proton channel and will facilitate rational design of new inhibitors. In this study, we determine the polar amine direction using M2TM reconstituted in lipid bilayers as well as dodecylphosphocholine (DPC) micelles. (13)C-(2)H rotational-echo double-resonance NMR experiments of (13)C-labeled M2TM and methyl-deuterated rimantadine in lipid bilayers showed that the polar amine pointed to the C-terminus of the channel, with the methyl group close to Gly34. Solution NMR experiments of M2TM in DPC micelles indicate that drug binding causes significant chemical shift perturbations of the protein that are very similar to those seen for M2TM and M2(18-60) bound to lipid bilayers. Specific (2)H-labeling of the drugs permitted the assignment of drug-protein cross peaks, which indicate that amantadine and rimantadine bind to the pore in the same fashion as for bilayer-bound M2TM. These results strongly suggest that adamantyl inhibition of M2TM is achieved not only by direct physical occlusion of the channel, but also by perturbing the equilibrium constant of the proton-sensing residue His37. The reproduction of the pharmacologically relevant specific pore-binding site in DPC micelles, which was not observed with a different detergent, DHPC, underscores the significant influence of the detergent environment on the functional structure of this membrane protein.

PMID: 21381693 [PubMed - as supplied by publisher]



Source: PubMed
Reply With Quote


Did you find this post helpful? Yes | No

Reply
Similar Threads
Thread Thread Starter Forum Replies Last Post
Proton-Detected Solid-State NMR Reveals Intramembrane Polar Networks in a Seven-Helical Transmembrane Protein Proteorhodopsin
Proton-Detected Solid-State NMR Reveals Intramembrane Polar Networks in a Seven-Helical Transmembrane Protein Proteorhodopsin Meaghan E. Ward, Lichi Shi, Evelyn Lake, Sridevi Krishnamurthy, Howard Hutchins, Leonid S. Brown and Vladimir Ladizhansky http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja207137h/aop/images/medium/ja-2011-07137h_0008.gif Journal of the American Chemical Society DOI: 10.1021/ja207137h http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA http://feeds.feedburner.com/~r/acs/jacsat/~4/Vzwkh1cjxOU
nmrlearner Journal club 0 10-09-2011 06:15 AM
Specific Binding of Adamantane Drugs and Direction of Their Polar Amines in the Pore of the Influenza M2 Transmembrane Domain in Lipid Bilayers and Dodecylphosphocholine Micelles Determined by NMR Spectroscopy
Specific Binding of Adamantane Drugs and Direction of Their Polar Amines in the Pore of the Influenza M2 Transmembrane Domain in Lipid Bilayers and Dodecylphosphocholine Micelles Determined by NMR Spectroscopy Sarah D. Cady, Jun Wang, Yibing Wu, William F. DeGrado and Mei Hong http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja102581n/aop/images/medium/ja-2010-02581n_0011.gif Journal of the American Chemical Society DOI: 10.1021/ja102581n http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA...
nmrlearner Journal club 0 03-08-2011 04:02 AM
Structure and dynamics of the lipid modifications of a transmembrane ?-helical peptide determined by (2)H solid-state NMR spectroscopy.
Structure and dynamics of the lipid modifications of a transmembrane ?-helical peptide determined by (2)H solid-state NMR spectroscopy. Structure and dynamics of the lipid modifications of a transmembrane ?-helical peptide determined by (2)H solid-state NMR spectroscopy. Biochim Biophys Acta. 2010 Dec 28; Authors: Penk A, Müller M, Scheidt HA, Langosch D, Huster D The fusion of biological membranes is mediated by integral membrane proteins with ?-helical transmembrane segments. Additionally, those proteins are often modified by the covalent...
nmrlearner Journal club 0 01-05-2011 09:51 PM
[NMR paper] Membrane protein-lipid interactions in mixed micelles studied by NMR spectroscopy wit
Membrane protein-lipid interactions in mixed micelles studied by NMR spectroscopy with the use of paramagnetic reagents. Related Articles Membrane protein-lipid interactions in mixed micelles studied by NMR spectroscopy with the use of paramagnetic reagents. Chembiochem. 2004 Apr 2;5(4):467-73 Authors: Hilty C, Wider G, Fernández C, Wüthrich K For solution NMR studies of the structure and function of membrane proteins, these macromolecules have to be reconstituted and solubilized in detergent micelles. Detailed characterization of the mixed...
nmrlearner Journal club 0 11-24-2010 09:51 PM
[NMR paper] Transmembrane domain of M2 protein from influenza A virus studied by solid-state (15)
Transmembrane domain of M2 protein from influenza A virus studied by solid-state (15)N polarization inversion spin exchange at magic angle NMR. Related Articles Transmembrane domain of M2 protein from influenza A virus studied by solid-state (15)N polarization inversion spin exchange at magic angle NMR. Biophys J. 2000 Aug;79(2):767-75 Authors: Song Z, Kovacs FA, Wang J, Denny JK, Shekar SC, Quine JR, Cross TA The M2 protein from the influenza A virus forms a proton channel in the virion that is essential for infection. This tetrameric protein...
nmrlearner Journal club 0 11-19-2010 08:29 PM
[Structural studies on transmembrane peptides in lipid bilayers using solid state NMR
Related Articles Seikagaku. 2010 Jun;82(6):498-504 Authors: Sato T, Aimoto S PMID: 20662258
nmrlearner Journal club 0 10-12-2010 02:52 PM
[NMR paper] Oligomerization of the EGF receptor transmembrane domain: a 2H NMR study in lipid bil
Oligomerization of the EGF receptor transmembrane domain: a 2H NMR study in lipid bilayers. http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-acspubs.jpg Related Articles Oligomerization of the EGF receptor transmembrane domain: a 2H NMR study in lipid bilayers. Biochemistry. 1997 Oct 14;36(41):12616-24 Authors: Jones DH, Rigby AC, Barber KR, Grant CW During the course of a previous study by wideline 2H NMR, we noted spectral features suggesting the possibility of monitoring homodimer/oligomer interactions between...
nmrlearner Journal club 0 08-22-2010 05:08 PM
[NMR paper] Structure of the Ras-binding domain of c-Raf-1 as determined by NMR spectroscopy and
Structure of the Ras-binding domain of c-Raf-1 as determined by NMR spectroscopy and identification of the region that interacts with Ras. Related Articles Structure of the Ras-binding domain of c-Raf-1 as determined by NMR spectroscopy and identification of the region that interacts with Ras. Drug Des Discov. 1996 Apr;13(3-4):83-93 Authors: Emerson SD, Madison VS, Palermo RE, Waugh DS, Scheffler JE, Tsao KL, Kiefer SE, Liu SP, Fry DC The structure of the Ras-binding domain of human c-Raf-1 (residues 55 to 132) as determined in solution by NMR...
nmrlearner Journal club 0 08-22-2010 02:27 PM


Thread Tools Search this Thread
Search this Thread:

Advanced Search
Display Modes Rate This Thread
Rate This Thread:

Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

BB code is On
Smilies are On
[IMG] code is On
HTML code is On
Trackbacks are Off
Pingbacks are Off
Refbacks are Off



BioNMR advertisements to pay for website hosting and domain registration. Nobody does it for us.



Powered by vBulletin® Version 3.7.3
Copyright ©2000 - 2024, Jelsoft Enterprises Ltd.
Copyright, BioNMR.com, 2003-2013
Search Engine Friendly URLs by vBSEO 3.6.0

All times are GMT. The time now is 02:15 AM.


Map