Related ArticlesNMR Methods for Detection of Small Molecule Binding to RGS4.
Methods Enzymol. 2013;522:133-52
Authors: Storaska AJ, Neubig RR
Abstract
The duration and amplitude of G-protein-coupled receptor (GPCR) signaling is controlled by regulator of G-protein signaling (RGS) proteins. The 20 RGS family members act as GTPase accelerating proteins through their interaction with the G? subunit of the G??? heterotrimer. Their influence over GPCR signaling has attracted many to these proteins as advantageous therapeutic targets. The nature of the RGS structure has proven to be difficult to target with small molecules using traditional high-throughput screening methods. This chapter describes NMR methods for studying small molecule interactions on RGS4. These methods can detect ligand binding without the requirement for an effect on protein function. Furthermore, the sensitivity of NMR permits detection of weaker protein-ligand interactions, such as those found with smaller fragment compounds. Fragment-based screening may be path forward to identifying a number of active small molecules toward RGS proteins. Methods and considerations for running a fragment-based screen on RGS4 using NMR are outlined in this section.
[CNS Yahoo group] How to add bond between protein residue and a small molecule in CNS
How to add bond between protein residue and a small molecule in CNS
Dear All, I'm stuck in a step where in i need to connect a bond an amino acid residue and a small molecule in CNS Thank you. Joseph
More...
nmrlearner
News from other NMR forums
0
08-07-2011 01:35 AM
Understanding small-molecule binding to MDM2: insights into structural effects of isoindolinone inhibitors from NMR spectroscopy.
Understanding small-molecule binding to MDM2: insights into structural effects of isoindolinone inhibitors from NMR spectroscopy.
Understanding small-molecule binding to MDM2: insights into structural effects of isoindolinone inhibitors from NMR spectroscopy.
Chem Biol Drug Des. 2011 May;77(5):301-8
Authors: Riedinger C, Noble ME, Wright DJ, Mulks F, Hardcastle IR, Endicott JA, McDonnell JM
The interaction between murine double minute (MDM2) and p53 is a major target in anticancer drug design. Several potent compound series, including the nutlins...
nmrlearner
Journal club
0
08-05-2011 11:48 AM
[Question from NMRWiki Q&A forum] About paragnetic impurities, inorganic salts, bad workups, etc. and their impact on small-molecule NMR spectra
About paragnetic impurities, inorganic salts, bad workups, etc. and their impact on small-molecule NMR spectra
I sometimes face the challenge of explaining to my organic chemists that, even if no impurity signals are visible in their 1H spectrum, other signs (like FID shape, very poor s/n compared to what could be expected with the sample qty, broad peaks, bad resolution...) indicate that clearly, something is wrong with their sample.
Everybody would agree that it's way much easier to convince an invidual based on concrete facts ("look, here we can see solvent/starting material/side...
nmrlearner
News from other NMR forums
0
03-31-2011 09:21 PM
[NMR paper] Determining the optimal size of small molecule mixtures for high throughput NMR scree
Determining the optimal size of small molecule mixtures for high throughput NMR screening.
Related Articles Determining the optimal size of small molecule mixtures for high throughput NMR screening.
J Biomol NMR. 2005 Mar;31(3):243-58
Authors: Mercier KA, Powers R
High-throughput screening (HTS) using NMR spectroscopy has become a common component of the drug discovery effort and is widely used throughout the pharmaceutical industry. NMR provides additional information about the nature of small molecule-protein interactions compared to...
nmrlearner
Journal club
0
11-24-2010 11:14 PM
[NMR paper] NMR structure of a complex between MDM2 and a small molecule inhibitor.
NMR structure of a complex between MDM2 and a small molecule inhibitor.
Related Articles NMR structure of a complex between MDM2 and a small molecule inhibitor.
J Biomol NMR. 2004 Oct;30(2):163-73
Authors: Fry DC, Emerson SD, Palme S, Vu BT, Liu CM, Podlaski F
MDM2 is a regulator of cell growth processes that acts by binding to the tumor suppressor protein p53 and ultimately restraining its activity. While inactivation of p53 by mutation is commonly observed in human cancers, a substantial percentage of tumors express wild type p53. In many of...
nmrlearner
Journal club
0
11-24-2010 10:01 PM
[NMR paper] NMR structure of free RGS4 reveals an induced conformational change upon binding Galp
NMR structure of free RGS4 reveals an induced conformational change upon binding Galpha.
Related Articles NMR structure of free RGS4 reveals an induced conformational change upon binding Galpha.
Biochemistry. 2000 Jun 20;39(24):7063-73
Authors: Moy FJ, Chanda PK, Cockett MI, Edris W, Jones PG, Mason K, Semus S, Powers R
Heterotrimeric guanine nucleotide-binding proteins (G-proteins) are transducers in many cellular transmembrane signaling systems where regulators of G-protein signaling (RGS) act as attenuators of the G-protein signal cascade...
nmrlearner
Journal club
0
11-18-2010 09:15 PM
Novel Small Molecule Inhibitors of MDR Mycobacterium tuberculosis by NMR Fragment Scr
Novel Small Molecule Inhibitors of MDR Mycobacterium tuberculosis by NMR Fragment Screening of Antigen 85C.
Related Articles Novel Small Molecule Inhibitors of MDR Mycobacterium tuberculosis by NMR Fragment Screening of Antigen 85C.
J Med Chem. 2010 Nov 12;
Authors: Scheich C, Puetter V, Schade M
Protein target-based discovery of novel antibiotics has been largely unsuccessful despite rich genome information. Particularly in need are new antibiotics for tuberculosis, which kills 1.6 million people annually and shows a rapid increase in...
nmrlearner
Journal club
0
11-16-2010 04:13 PM
Small Molecule NMR Scientist (B.S./ M.S.) at Novartis Ag (Cambridge, MA)
Small Molecule NMR Scientist (B.S./ M.S.) at Novartis Ag (Cambridge, MA)
using the state-of-the-art NMR methodologies. As an NMR scientist within the team, you will be responsible for ... in small molecular NMR with demonstrated success in modern NMR methodologies. Demonstrated skills in data collection...
More...
NMR Methods for Detection of Small Molecule Binding to RGS4.
Linear Mode
