[NMR paper] Solid phase synthesis, NMR structure determination of ?-KTx3.8, its in silico docking to Kv1.x potassium channels, and electrophysiological analysis provide insights into toxin-channel selectivity.
Solid phase synthesis, NMR structure determination of ?-KTx3.8, its in silico docking to Kv1.x potassium channels, and electrophysiological analysis provide insights into toxin-channel selectivity.
Related ArticlesSolid phase synthesis, NMR structure determination of ?-KTx3.8, its in silico docking to Kv1.x potassium channels, and electrophysiological analysis provide insights into toxin-channel selectivity.
Toxicon. 2015 May 5;
Authors: Kohl B, Rothenberg I, Ali SA, Alam M, Seebohm G, Kalbacher H, Voelter W, Stoll R
Abstract
Animal venoms, such as those from scorpions, are a potent source for new pharmacological substances. In this study we have determined the structure of the ?-KTx3.8 (named as Bs6) scorpion toxin by multidimensional protonhomonuclear NMR spectroscopy and investigated its function by molecular dynamics (MD) simulations and electrophysiological measurements. Bs6 is a potent inhibitor of the Kv1.3 channel which plays an important role during the activation and proliferation of memory T-cells (TEM), which play an important role in autoimmune diseases. Therefore, it could be an interesting target for treatment of autoimmune diseases. In this study, Bs6 was synthesised by solid-phase synthesis and its three-dimensional (3D) structure has been determined. To gain a deeper insight into the interaction of Bs6 with different potassium channels like hKv1.1 and hKv1.3, the protein-protein complex was modelled based on known toxin-channel structures and tested for stability in MD simulations using GROMACS. The toxin-channel interaction was further analysed by electrophysiological measurements of different potassium channels like hKv1.3 and hKv7.1. As potassium channel inhibitors could play an important role to overcome autoimmune diseases like multiple sclerosis and type-1 diabetes mellitus, our data contribute to the understanding of the molecular mechanism of action and will ultimately help to develop new potent inhibitors in future.
PMID: 25953725 [PubMed - as supplied by publisher]
[NMR paper] Defining the Potential of Aglycone Modifications for Affinity/Selectivity Enhancement against Medically Relevant Lectins: Synthesis, Activity Screening, and HSQC-Based NMR Analysis.
Defining the Potential of Aglycone Modifications for Affinity/Selectivity Enhancement against Medically Relevant Lectins: Synthesis, Activity Screening, and HSQC-Based NMR Analysis.
Related Articles Defining the Potential of Aglycone Modifications for Affinity/Selectivity Enhancement against Medically Relevant Lectins: Synthesis, Activity Screening, and HSQC-Based NMR Analysis.
Chembiochem. 2014 Nov 18;
Authors: Rauthu SR, Shiao TC, André S, Miller MC, Madej E, Mayo KH, Gabius HJ, Roy R
Abstract
The emerging significance of...
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[NMR paper] Protein Structure Determination by Magic-Angle Spinning Solid-State NMR, and Insights into the Formation, Structure, and Stability of Amyloid Fibrils.
Protein Structure Determination by Magic-Angle Spinning Solid-State NMR, and Insights into the Formation, Structure, and Stability of Amyloid Fibrils.
Related Articles Protein Structure Determination by Magic-Angle Spinning Solid-State NMR, and Insights into the Formation, Structure, and Stability of Amyloid Fibrils.
Annu Rev Biophys. 2013 Mar 22;
Authors: Comellas G, Rienstra CM
Abstract
Protein structure determination methods using magic-angle spinning solidstate nuclear magnetic resonance (MAS SSNMR) have experienced a remarkable...
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[NMR paper] An NMR investigation of the structure, function and role of the hERG channel selectivity filter in the long QT syndrome.
An NMR investigation of the structure, function and role of the hERG channel selectivity filter in the long QT syndrome.
Related Articles An NMR investigation of the structure, function and role of the hERG channel selectivity filter in the long QT syndrome.
Biochim Biophys Acta. 2013 Mar 5;
Authors: Gravel AE, Arnold AA, Dufourc EJ, Marcotte I
Abstract
The human ether-a-go-go-related gene (hERG) voltage-gated K+ channels are located in heart cell membranes and hold a unique selectivity filter (SF) amino acid sequence (SVGFG) as compared...
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Revealing Protein Structures in Solid-Phase Peptide Synthesis by 13C Solid-State NMR: Evidence of Excessive Misfolding for Alzheimer’s ?
Revealing Protein Structures in Solid-Phase Peptide Synthesis by 13C Solid-State NMR: Evidence of Excessive Misfolding for Alzheimer’s ?
Songlin Wang and Yoshitaka Ishii
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja212190z/aop/images/medium/ja-2011-12190z_0002.gif
Journal of the American Chemical Society
DOI: 10.1021/ja212190z
http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA
http://feeds.feedburner.com/~r/acs/jacsat/~4/6EE7uthrnLg
[NMR paper] Saturation transfer difference (STD) 1H-NMR experiments and in silico docking experim
Saturation transfer difference (STD) 1H-NMR experiments and in silico docking experiments to probe the binding of N-acetylneuraminic acid and derivatives to Vibrio cholerae sialidase.
Related Articles Saturation transfer difference (STD) 1H-NMR experiments and in silico docking experiments to probe the binding of N-acetylneuraminic acid and derivatives to Vibrio cholerae sialidase.
Proteins. 2004 Aug 1;56(2):346-53
Authors: Haselhorst T, Wilson JC, Thomson RJ, McAtamney S, Menting JG, Coppel RL, von Itzstein M
Saturation transfer difference...
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[NMR paper] A novel potassium channel blocking toxin from the scorpion Pandinus imperator: A 1H N
A novel potassium channel blocking toxin from the scorpion Pandinus imperator: A 1H NMR analysis using a nano-NMR probe.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-acspubs.jpg Related Articles A novel potassium channel blocking toxin from the scorpion Pandinus imperator: A 1H NMR analysis using a nano-NMR probe.
Biochemistry. 1997 Mar 4;36(9):2649-58
Authors: Delepierre M, Prochnicka-Chalufour A, Possani LD
The three-dimensional solution structure of a novel peptide, Pi 1, purified from the venom of the...
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08-22-2010 03:31 PM
[NMR paper] A novel potassium channel blocking toxin from the scorpion Pandinus imperator: A 1H N
A novel potassium channel blocking toxin from the scorpion Pandinus imperator: A 1H NMR analysis using a nano-NMR probe.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-acspubs.jpg Related Articles A novel potassium channel blocking toxin from the scorpion Pandinus imperator: A 1H NMR analysis using a nano-NMR probe.
Biochemistry. 1997 Mar 4;36(9):2649-58
Authors: Delepierre M, Prochnicka-Chalufour A, Possani LD
The three-dimensional solution structure of a novel peptide, Pi 1, purified from the venom of the...
Solid phase synthesis, NMR structure determination of ?-KTx3.8, its in silico docking to Kv1.x potassium channels, and electrophysiological analysis provide insights into toxin-channel selectivity.
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