Related ArticlesDrug screening strategy for human membrane proteins: from NMR protein backbone structure to in silica- and NMR-screened hits.
Biochem Biophys Res Commun. 2014 Feb 10;
Authors: Lindert S, Maslennikov I, Chiu E, Pierce LC, Andrew McCammon J, Choe S
Abstract
About 8,000 genes encode membrane proteins in the human genome. The information about their druggability will be very useful to facilitate drug discovery and development. The main problem, however, consists of limited structural and functional information about these proteins because they are difficult to produce biochemically and to study. In this paper we describe the strategy that combines Cell-free protein expression, NMR spectroscopy, and molecular DYnamics simulation (CNDY) techniques. Results of a pilot CNDY experiment provide us with a guiding light towards expedited identification of the hit compounds against a new uncharacterized membrane protein as a potentially druggable target. These hits can then be further characterized and optimized to develop the initial lead compound quicker. We illustrate such "omics" approach for drug discovery with the CNDY strategy applied to two example proteins: hypoxia-induced genes HIGD1A and HIGD1B.
PMID: 24525125 [PubMed - as supplied by publisher]
Drug screening strategy for human membrane proteins: from NMR protein backbone structure to in silica- and NMR-screened hits
Drug screening strategy for human membrane proteins: from NMR protein backbone structure to in silica- and NMR-screened hits
Publication date: Available online 10 February 2014
Source:Biochemical and Biophysical Research Communications</br>
Author(s): Steffen Lindert , Innokentiy Maslennikov , Ellis Chiu , Levi C Pierce , J. Andrew McCammon , Senyon Choe</br>
About 8,000 genes encode membrane proteins in the human genome. The information about their druggability will be very useful to facilitate drug discovery and development. The main problem, however,...
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02-10-2014 08:46 PM
[NMR paper] Solid State NMR Strategy for Characterizing Native Membrane Protein Structures.
Solid State NMR Strategy for Characterizing Native Membrane Protein Structures.
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Acc Chem Res. 2013 Mar 7;
Authors: Murray DT, Das N, Cross TA
Abstract
Unlike water soluble proteins, the structures of helicaltransmembrane proteins depend on a very complex environment. These proteins sit in the midst of dramatic electrical and chemical gradients and are often subject to variations in the lateral pressure profile, order parameters, dielectric...
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03-09-2013 11:05 AM
An NMR strategy for fragment-based ligand screening utilizing a paramagnetic lanthanide probe.
An NMR strategy for fragment-based ligand screening utilizing a paramagnetic lanthanide probe.
An NMR strategy for fragment-based ligand screening utilizing a paramagnetic lanthanide probe.
J Biomol NMR. 2011 Sep 17;
Authors: Saio T, Ogura K, Shimizu K, Yokochi M, Burke TR, Inagaki F
Abstract
A nuclear magnetic resonance-based ligand screening strategy utilizing a paramagnetic lanthanide probe is presented. By fixing a paramagnetic lanthanide ion to a target protein, a pseudo-contact shift (PCS) and a paramagnetic relaxation...
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09-20-2011 03:10 PM
An NMR strategy for fragment-based ligand screening utilizing a paramagnetic lanthanide probe
An NMR strategy for fragment-based ligand screening utilizing a paramagnetic lanthanide probe
Abstract A nuclear magnetic resonance-based ligand screening strategy utilizing a paramagnetic lanthanide probe is presented. By fixing a paramagnetic lanthanide ion to a target protein, a pseudo-contact shift (PCS) and a paramagnetic relaxation enhancement (PRE) can be observed for both the target protein and its bound ligand. Based on PRE and PCS information, the bound ligand is then screened from the compound library and the structure of the ligandâ??protein complex is determined. PRE is an...
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09-20-2011 05:02 AM
[NMR paper] Membrane protein preparation for TROSY NMR screening.
Membrane protein preparation for TROSY NMR screening.
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Methods Enzymol. 2005;394:321-34
Authors: Tian C, Karra MD, Ellis CD, Jacob J, Oxenoid K, Sönnichsen F, Sanders CR
The first steps toward undertaking an NMR structural study of a new protein is very often to purify the protein and then to acquire an HSQC or TROSY NMR spectrum, the quality of which is used to assess the feasibility of an NMR-based structural determination. Relatively few integral membrane proteins (IMPs)...
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11-24-2010 11:14 PM
[NMR paper] Expression screening, protein purification and NMR analysis of human protein domains
Expression screening, protein purification and NMR analysis of human protein domains for structural genomics.
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J Struct Funct Genomics. 2004;5(1-2):119-31
Authors: Folkers GE, van Buuren BN, Kaptein R
Structural genomics, the determination of protein structures on a genome-wide scale, is still in its infancy for eukaryotes due to the number and size of their genes. Low protein expression and solubility of eukaryotic...
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[NMR paper] Site-directed 13C solid-state NMR studies on membrane proteins: strategy and goals to
Site-directed 13C solid-state NMR studies on membrane proteins: strategy and goals toward revealing conformation and dynamics as illustrated for bacteriorhodopsin labeled with amino acid residues.
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Magn Reson Chem. 2004 Feb;42(2):218-30
Authors: Saitô H, Mikami J, Yamaguchi S, Tanio M, Kira A, Arakawa T, Yamamoto K, Tuzi S
We have so...
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[NMR paper] The SHAPES strategy: an NMR-based approach for lead generation in drug discovery.
The SHAPES strategy: an NMR-based approach for lead generation in drug discovery.
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Chem Biol. 1999 Oct;6(10):755-69
Authors: Fejzo J, Lepre CA, Peng JW, Bemis GW, Ajay , Murcko MA, Moore JM
BACKGROUND: Recently, it has been shown that nuclear magnetic resonance (NMR) may be used to identify ligands that bind to low molecular weight protein drug targets. Recognizing the utility of NMR as a very sensitive method for detecting binding, we have...
Drug screening strategy for human membrane proteins: from NMR protein backbone structure to in silica- and NMR-screened hits.
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