Related ArticlesMechanistic insight into inhibition of two-component system signaling.
Medchemcomm. 2013;4(1):269-277
Authors: Francis S, Wilke KE, Brown DE, Carlson EE
Abstract
Two-component signal transduction systems (TCSs) are commonly used by bacteria to couple environmental stimuli to adaptive responses. Targeting the highly conserved kinase domain in these systems represents a promising strategy for the design of a broad-spectrum antibiotic; however, development of such compounds has been marred by an incomplete understanding of the conserved binding features within the active site that could be exploited in molecule design. Consequently, a large percentage of the available TCS inhibitors demonstrate poor target specificity and act via multiple mechanisms, with aggregation of the kinase being the most notable. In order to elucidate the mode of action of some of these compounds, molecular modeling was employed to dock a suite of molecules into the ATP-binding domain of several histidine kinases. This effort revealed a key structural feature of the domain that is likely interacting with several known inhibitors and is also highly conserved. Furthermore, generation of several simplified scaffolds derived from a reported inhibitor and characterization of these compounds using activity assays, protein aggregation studies and saturation transfer differential (STD) NMR suggests that targeting of this protein feature may provide a basis for the design of ATP-competitive compounds.
PMID: 23336064 [PubMed - as supplied by publisher]
Post Doc - Mechanistic drivers of receptor pharmacology by NMR ...
Post Doc - Mechanistic drivers of receptor pharmacology by NMR ...
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Cell signaling, post-translational protein modifications and NMR spectroscopy
Cell signaling, post-translational protein modifications and NMR spectroscopy
Abstract Post-translationally modified proteins make up the majority of the proteome and establish, to a large part, the impressive level of functional diversity in higher, multi-cellular organisms. Most eukaryotic post-translational protein modifications (PTMs) denote reversible, covalent additions of small chemical entities such as phosphate-, acyl-, alkyl- and glycosyl-groups onto selected subsets of modifiable amino acids. In turn, these modifications induce highly specific changes in the chemical ...
[NMR paper] Three-dimensional solution structure of the calcium-signaling protein apo-S100A1 as d
Three-dimensional solution structure of the calcium-signaling protein apo-S100A1 as determined by NMR.
Related Articles Three-dimensional solution structure of the calcium-signaling protein apo-S100A1 as determined by NMR.
Biochemistry. 2002 Jan 22;41(3):788-96
Authors: Rustandi RR, Baldisseri DM, Inman KG, Nizner P, Hamilton SM, Landar A, Landar A, Zimmer DB, Weber DJ
S100A1, a member of the S100 protein family, is an EF-hand containing Ca(2+)-binding protein (93 residues per subunit) with noncovalent interactions at its dimer interface. Each...
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11-24-2010 08:49 PM
[NMR paper] Insight into the mechanism of serpin-proteinase inhibition from 2D [1H-15N] NMR studi
Insight into the mechanism of serpin-proteinase inhibition from 2D NMR studies of the 69 kDa alpha 1-proteinase inhibitor Pittsburgh-trypsin covalent complex.
Related Articles Insight into the mechanism of serpin-proteinase inhibition from 2D NMR studies of the 69 kDa alpha 1-proteinase inhibitor Pittsburgh-trypsin covalent complex.
Biochemistry. 2001 May 29;40(21):6284-92
Authors: Peterson FC, Gettins PG
We have used -HSQC NMR to investigate the structural changes that occur in both serpin and proteinase in forming the kinetically trapped...
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11-19-2010 08:32 PM
[NMR paper] Backbone dynamics of the calcium-signaling protein apo-S100B as determined by 15N NMR
Backbone dynamics of the calcium-signaling protein apo-S100B as determined by 15N NMR relaxation.
Related Articles Backbone dynamics of the calcium-signaling protein apo-S100B as determined by 15N NMR relaxation.
Biochemistry. 2001 Mar 27;40(12):3439-48
Authors: Inman KG, Baldisseri DM, Miller KE, Weber DJ
Backbone dynamics of homodimeric apo-S100B were studied by (15)N nuclear magnetic resonance relaxation at 9.4 and 14.1 T. Longitudinal relaxation (T(1)), transverse relaxation (T(2)), and the (15)N- NOE were measured for 80 of 91 backbone...
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[NMR paper] NMR structure of phospho-tyrosine signaling complexes.
NMR structure of phospho-tyrosine signaling complexes.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www3.interscience.wiley.com-aboutus-images-wiley_interscience_pubmed_logo_120x27.gif Related Articles NMR structure of phospho-tyrosine signaling complexes.
Med Res Rev. 1999 Jul;19(4):295-305
Authors: Post CB, Gaul BS, Eisenmesser EZ, Schneider ML
A structural basis for activation and substrate specificity of src tyrosine kinases, and regulation of protein-protein association by tyrosine phosphorylation is described. Lyn, a...
Mechanistic insight into inhibition of two-component system signaling.
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