Search results for "binding site"
showing 10 items of 856 documents
The C-terminal region of human plasma fetuin-B is dispensable for the raised-elephant-trunk mechanism of inhibition of astacin metallopeptidases
2019
© The Author(s) 2019.
Searching for Chymase Inhibitors among Chamomile Compounds Using a Computational-Based Approach
2018
Inhibitors of chymase have good potential to provide a novel therapeutic approach for the treatment of cardiovascular diseases. We used a computational approach based on pharmacophore modeling, docking, and molecular dynamics simulations to evaluate the potential ability of 13 natural compounds from chamomile extracts to bind chymase enzyme. The results indicated that some chamomile compounds can bind to the active site of human chymase. In particular, chlorogenic acid had a predicted binding energy comparable or even better than that of some known chymase inhibitors, interacted stably with key amino acids in the chymase active site, and appeared to be more selective for chymase than other …
The Crystal Structure of Gurmarin, a Sweet Taste–Suppressing Protein: Identification of the Amino Acid Residues Essential for Inhibition
2018
International audience; Gurmarin is a highly specific sweet-taste suppressing protein in rodents that is isolated from the Indian plant Gymnemasylvestre. Gurmarin consists of 35 amino acid residues containing three intramolecular disulfide bridges that form a cystine knot. Here, we report the crystal structure of gurmarin at a 1.45 Å resolution and compare it with previously reported NMR solution structures. The atomic structure at this resolution allowed us to identify a very flexible region consisting of hydrophobic residues. Some of these amino acid residues had been identified as a putative binding site for the rat sweet taste receptor in a previous study. By combining alanine-scanning …
Evaluating the stability of pharmacophore features using molecular dynamics simulations.
2016
Abstract Molecular dynamics simulations of twelve protein—ligand systems were used to derive a single, structure based pharmacophore model for each system. These merged models combine the information from the initial experimental structure and from all snapshots saved during the simulation. We compared the merged pharmacophore models with the corresponding PDB pharmacophore models, i.e., the static models generated from an experimental structure in the usual manner. The frequency of individual features, of feature types and the occurrence of features not present in the static model derived from the experimental structure were analyzed. We observed both pharmacophore features not visible in …
Regulatory network analysis in estradiol-treated human endothelial cells.
2021
Background/Aims: Estrogen has been reported to have beneficial effects on vascular biology through direct actions on endothelium. Together with transcription factors, miRNAs are the major drivers of gene expression and signaling networks. The objective of this study was to identify a com-prehensive regulatory network (miRNA-transcription factor-downstream genes) that controls the transcriptomic changes observed in endothelial cells exposed to estradiol. Methods: miR-NA/mRNA interactions were assembled using our previous microarray data of human umbilical vein endothelial cells (HUVEC) treated with 17ß- Estradiol (E2) (1 nmol/lL, 24 h). miRNA--mRNA pairings and their associated canonical pat…
Mechanism and biological role of Dnmt2 in Nucleic Acid Methylation
2016
ABSTRACT A group of homologous nucleic acid modification enzymes called Dnmt2, Trdmt1, Pmt1, DnmA, and Ehmet in different model organisms catalyze the transfer of a methyl group from the cofactor S-adenosyl-methionine (SAM) to the carbon-5 of cytosine residues. Originally considered as DNA MTases, these enzymes were shown to be tRNA methyltransferases about a decade ago. Between the presumed involvement in DNA modification-related epigenetics, and the recent foray into the RNA modification field, significant progress has characterized Dnmt2-related research. Here, we review this progress in its diverse facets including molecular evolution, structural biology, biochemistry, chemical biology,…
A protein-RNA interaction atlas of the ribosome biogenesis factor AATF
2018
AbstractAATF is a central regulator of the cellular outcome upon p53 activation, a finding that has primarily been attributed to its function as a transcription factor. Recent data showed that AATF is essential for ribosome biogenesis and plays a role in rRNA maturation. AATF has been implicated to fulfil this role through direct interaction with rRNA and was identified in several RNA-interactome capture experiments. Here, we provide a first comprehensive analysis of the RNA bound by AATF using CLIP-sequencing. Interestingly, this approach shows predominant binding of the 45S pre-ribosomal RNA precursor molecules. Furthermore, AATF binds to mRNAs encoding for ribosome biogenesis factors as …
Structure-Based Discovery of Small Molecules Binding to RNA
2017
Ribonucleic acids (RNAs) constitute attractive drug targets. The wealth of structural information about RNAs is steadily increasing making it possible to use this information for the design of new ligands. Two methods that make heavy use of structural knowledge for ligand discovery are molecular docking and fragment screening. In molecular docking the structure of the binding site is used as a template for the design of new ligands using computational methods whereas in fragment screening biophysical methods are used for the detection of weak binding ligands which are subsequently elaborated into tighter binding molecules. In this chapter, we give an overview of both methods in the context …
Interaction between ROR1 and MuSK activation complex in myogenic cells
2017
The ROR family of receptor tyrosine kinases, ROR1 and ROR2, is known to play an important role during skeletal muscle regeneration. ROR1 has a critical role in regulating satellite cell (SC) proliferation during muscle regeneration, and proinflammatory cytokines such as TNF-α and IL-1β can induce expression of ROR1 in myogenic cells via NF-κB activation. While searching for ROR1-interacting proteins in myogenic cells, we identified MuSK as a ROR1-binding protein. MuSK interacts with and phosphorylates ROR1 at the cytoplasmic proline-rich domain. ROR1 also interacts with the MuSK activator Dok-7 independently of MuSK interaction. Collectively, our results identified ROR1 as a new interacting…
Super-resolution binding activated localization microscopy through reversible change of DNA conformation
2018
ABSTRACT Methods of super-resolving light microscopy (SRM) have found an exponentially growing range of applications in cell biology, including nuclear structure analyses. Recent developments have proven that Single Molecule Localization Microscopy (SMLM), a type of SRM, is particularly useful for enhanced spatial analysis of the cell nucleus due to its highest resolving capability combined with very specific fluorescent labeling. In this commentary we offer a brief review of the latest methodological development in the field of SMLM of chromatin designated DNA Structure Fluctuation Assisted Binding Activated Localization Microscopy (abbreviated as fBALM) as well as its potential future app…