Related ArticlesNMR-driven discovery of benzoylanthranilic acid inhibitors of far upstream element binding protein binding to the human oncogene c-myc promoter.
J Med Chem. 2004 Sep 23;47(20):4851-7
Authors: Huth JR, Yu L, Collins I, Mack J, Mendoza R, Isaac B, Braddock DT, Muchmore SW, Comess KM, Fesik SW, Clore GM, Levens D, Hajduk PJ
Reversal of aberrant gene expression that is induced by the proto-oncogene c-myc is likely to be effective for treating a variety of tumors that rely on this pathway for growth. One strategy to down-regulate the c-myc pathway is to target transcription factors that regulate its own expression. A host of proteins act in coordination to regulate c-myc expression and any one of them are theoretical targets for small-molecule therapy. Experimentally, it has been shown that the far upstream element (FUSE) binding protein (FBP) is essential for c-myc expression, and reductions in FBP levels both reduce c-myc expression and correlate with slower cell growth. FBP binds to ssDNA by capturing exposed DNA bases in a hydrophobic pocket. This suggests that a small molecule could be designed to occupy this pocket and inhibit FBP function. Using a variety of screening methodologies, we have identified ligands that bind to the DNA binding pockets of the KH domains of FBP. Gel shift analyses using full length FBP and a related transcription factor confirm that a small-molecule lead compound inhibits DNA binding in a specific manner. The benzoylanthranilic acid compounds described here represent leads in the design of FBP inhibitors that can serve as useful tools in the study of c-myc regulation and in the development of therapeutics that target the c-myc pathway.
A systematic mutagenesis-driven strategy for site-resolved NMR studies of supramolecular assemblies
A systematic mutagenesis-driven strategy for site-resolved NMR studies of supramolecular assemblies
Abstract Obtaining sequence-specific assignments remains a major bottleneck in solution NMR investigations of supramolecular structure, dynamics and interactions. Here we demonstrate that resonance assignment of methyl probes in high molecular weight protein assemblies can be efficiently achieved by combining fast NMR experiments, residue-type-specific isotope-labeling and automated site-directed mutagenesis. The utility of this general and straightforward strategy is demonstrated through...
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A systematic mutagenesis-driven strategy for site-resolved NMR studies of supramolecular assemblies.
A systematic mutagenesis-driven strategy for site-resolved NMR studies of supramolecular assemblies.
A systematic mutagenesis-driven strategy for site-resolved NMR studies of supramolecular assemblies.
J Biomol NMR. 2011 May 29;
Authors: Amero C, Asunción Durá M, Noirclerc-Savoye M, Perollier A, Gallet B, Plevin MJ, Vernet T, Franzetti B, Boisbouvier J
Obtaining sequence-specific assignments remains a major bottleneck in solution NMR investigations of supramolecular structure, dynamics and interactions. Here we demonstrate that resonance...
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06-01-2011 02:30 PM
[NMR paper] Real time NMR monitoring of local unfolding of HIV-1 protease tethered dimer driven b
Real time NMR monitoring of local unfolding of HIV-1 protease tethered dimer driven by autolysis.
Related Articles Real time NMR monitoring of local unfolding of HIV-1 protease tethered dimer driven by autolysis.
FEBS Lett. 2001 May 18;497(1):59-64
Authors: Panchal SC, Bhavesh NS, Hosur RV
Structural studies in proteases have been hampered because of their inherent autolytic function. However, since autolysis is known to be mediated via protein unfolding, careful monitoring of the autolytic reaction has the potential to throw light on the...
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11-19-2010 08:32 PM
[NMR paper] Mechanism of neomycin and Rev peptide binding to the Rev responsive element of HIV-1
Mechanism of neomycin and Rev peptide binding to the Rev responsive element of HIV-1 as determined by fluorescence and NMR spectroscopy.
Related Articles Mechanism of neomycin and Rev peptide binding to the Rev responsive element of HIV-1 as determined by fluorescence and NMR spectroscopy.
Biochemistry. 2000 May 16;39(19):5630-41
Authors: Lacourciere KA, Stivers JT, Marino JP
Rev is an essential HIV-1 regulatory protein that binds the Rev responsive element (RRE) within the env gene of the HIV-1 RNA genome and is involved in transport of...
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11-18-2010 09:15 PM
[NMR paper] NMR-based discovery of lead inhibitors that block DNA binding of the human papillomav
NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-acspubs.jpg Related Articles NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein.
J Med Chem. 1997 Sep 26;40(20):3144-50
Authors: Hajduk PJ, Dinges J, Miknis GF, Merlock M, Middleton T, Kempf DJ, Egan DA, Walter KA, Robins TS, Shuker SB, Holzman TF, Fesik SW
The E2 protein is required for the replication of human...
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08-22-2010 05:08 PM
[NMR paper] NMR analysis of CYP1(HAP1) DNA binding domain-CYC1 upstream activation sequence inter
NMR analysis of CYP1(HAP1) DNA binding domain-CYC1 upstream activation sequence interactions: recognition of a CGG trinucleotide and of an additional thymine 5 bp downstream by the zinc cluster and the N-terminal extremity of the protein.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final_free.gif http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.pubmedcentral.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.gif Related Articles NMR analysis of CYP1(HAP1) DNA binding domain-CYC1 upstream...
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08-22-2010 05:08 PM
[NMR paper] Assignment and modeling of the Rev Response Element RNA bound to a Rev peptide using
Assignment and modeling of the Rev Response Element RNA bound to a Rev peptide using 13C-heteronuclear NMR.
Related Articles Assignment and modeling of the Rev Response Element RNA bound to a Rev peptide using 13C-heteronuclear NMR.
J Biomol NMR. 1995 Dec;6(4):375-89
Authors: Battiste JL, Tan R, Frankel AD, Williamson JR
The Rev Response Element (RRE) RNA-Rev protein interaction is important for regulation of gene expression in the human immunodeficiency virus. A model system for this interaction, which includes stem IIB of the RRE RNA and an...
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08-22-2010 03:50 AM
[NMR paper] An NMR study of the HIV-1 TAR element hairpin.
An NMR study of the HIV-1 TAR element hairpin.
Related Articles An NMR study of the HIV-1 TAR element hairpin.
Biochemistry. 1993 Nov 23;32(46):12522-30
Authors: Jaeger JA, Tinoco I
The TAR hairpin is an important part of the 5' long terminal repeat of HIV-1 and appears to be recognized by a cellular protein. A 14-base model of the native TAR hairpin 5'-GAGC-GCUC-3' (loop bases in square brackets) has been studied by proton, phosphorus, and natural abundance carbon NMR; these results are compared to other published NMR studies of the TAR...
NMR-driven discovery of benzoylanthranilic acid inhibitors of far upstream element bi
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