Potential binding sites of the trans-activator FIS are present upstream of all rRNA operons and of many but not all tRNA operons

Urea is one of the most extensively used fertilizers in agriculture but has a detrimental impact on the environment. One of the strategies to reduce this impact can be engineering modified plants containing urease enzyme with a considerably higher affinity for urea so that the urea applied in the fields can be significantly reduced. In this study, we have selected Oryza sativa Urease and generated stable mutants having a high affinity for urea. We modeled the 3D structure of the enzyme and identified the potential binding sites by analyzing the binding sites of similar proteins, i.e., 48 urea binding proteins. We found that mutation of Arg578 with Cys near the substrate-binding site of Oryza sativa Urease leads to a stable mutant protein that has a higher binding affinity for urea. This study will lead to a generation of environment-friendly, stable, genetically modified rice crop that consumes lesser urea, without compromising with crop productivity.

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INSILICO STUDIES OF OXIME PRODRUG OF GLICLAZIDE AGAINST SULPHONYLUREA RECEPTORS (SUR 1)

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2017v9i4.20968 ◽

2017 ◽

Vol 9 (4) ◽

pp. 100

Author(s):

Surendran Vijayaraj ◽

Kannekanti Chaithanya Veena

Keyword(s):

Binding Sites ◽

Pancreatic Beta Cells ◽

Molecular Targets ◽

Docking Studies ◽

Docking Analysis ◽

Potential Binding ◽

In Silico Study ◽

Molecular Docking Analysis ◽

Autodock 4.2

Objective: Objective of the study is to perform a molecular docking analysis of novel oxime prodrug of gliclazide against SUR1 receptor.Methods: Sulfonylurea receptors (SUR) are membrane proteins which are the molecular targets of the sulfonylurea class of anti-diabetic drugs whose mechanism of action is to promote insulin release from pancreatic beta cells. Oxime prodrug of gliclazide a better soluble derivative of gliclazide is used for enhancement of bioavailability of gliclazide. Autodock 4.2 software was used for docking studies. Ligand 2D structures were drawn using ChemDraw Ultra 7.0. Binding sites, docking poses and interactions of the ligand with SUR1 receptors were studied by pymol software.Results: The docking studies suggest that potential binding sites of oxime prodrug of gliclazide exhibiting all the major interactions such as hydrogen bonding, hydrophobic interaction and electrostatic interaction with GLU43, LEU11, LEU 40, ILE17 GLU 68, GLN72 residues of SUR1. The binding energy of complexes are also found to be minimal forming stable complexes.Conclusion: In silico study of oxime prodrug of gliclazide conforms, the binding of oxime prodrug of glicalzide with SUR1 receptors which effectively controls the release insulin to regulate plasma glucose concentrations. Hence, the oxime prodrug of gliclazide could be a potent anti-diabetic target molecule which may be worth for further in vitro and in vivostudies.

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The Retinoid and Non-Retinoid Ligands of the Rod Visual G Protein-Coupled Receptor

International Journal of Molecular Sciences ◽

10.3390/ijms20246218 ◽

2019 ◽

Vol 20 (24) ◽

pp. 6218 ◽

Cited By ~ 1

Author(s):

Joseph T. Ortega ◽

Beata Jastrzebska

Keyword(s):

Drug Discovery ◽

G Protein ◽

Binding Sites ◽

Binding Pocket ◽

Biologically Active ◽

Surface Receptors ◽

Beneficial Effects ◽

Light Sensing ◽

Potential Binding ◽

G Protein Coupled

G protein-coupled receptors (GPCRs) play a predominant role in the drug discovery effort. These cell surface receptors are activated by a variety of specific ligands that bind to the orthosteric binding pocket located in the extracellular part of the receptor. In addition, the potential binding sites located on the surface of the receptor enable their allosteric modulation with critical consequences for their function and pharmacology. For decades, drug discovery focused on targeting the GPCR orthosteric binding sites. However, finding that GPCRs can be modulated allosterically opened a new venue for developing novel pharmacological modulators with higher specificity. Alternatively, focus on discovering of non-retinoid small molecules beneficial in retinopathies associated with mutations in rhodopsin is currently a fast-growing pharmacological field. In this review, we summarize the accumulated knowledge on retinoid ligands and non-retinoid modulators of the light-sensing GPCR, rhodopsin and their potential in combating the specific vision-related pathologies. Also, recent findings reporting the potential of biologically active compounds derived from natural products as potent rod opsin modulators with beneficial effects against degenerative diseases related to this receptor are highlighted here.

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DNA Binding Site Selection of Dimeric and Tetrameric Stat5 Proteins Reveals a Large Repertoire of Divergent Tetrameric Stat5a Binding Sites

Molecular and Cellular Biology ◽

10.1128/mcb.20.1.389-401.2000 ◽

2000 ◽

Vol 20 (1) ◽

pp. 389-401 ◽

Cited By ~ 128

Author(s):

Elisabetta Soldaini ◽

Susan John ◽

Stefano Moro ◽

Julie Bollenbacher ◽

Ulrike Schindler ◽

...

Keyword(s):

Binding Site ◽

Dna Sequences ◽

Site Selection ◽

Binding Sites ◽

Tetramer Binding ◽

Dna Binding Site ◽

Potential Binding ◽

Wide Range ◽

Large Repertoire ◽

Selection Of

ABSTRACT We have defined the optimal binding sites for Stat5a and Stat5b homodimers and found that they share similar core TTC(T/C)N(G/A)GAA interferon gamma-activated sequence (GAS) motifs. Stat5a tetramers can bind to tandemly linked GAS motifs, but the binding site selection revealed that tetrameric binding also can be seen with a wide range of nonconsensus motifs, which in many cases did not allow Stat5a binding as a dimer. This indicates a greater degree of flexibility in the DNA sequences that allow binding of Stat5a tetramers than dimers. Indeed, in an oligonucleotide that could bind both dimers and tetramers, it was possible to design mutants that affected dimer binding without affecting tetramer binding. A spacing of 6 bp between the GAS sites was most frequently selected, demonstrating that this distance is favorable for Stat5a tetramer binding. These data provide insights into tetramer formation by Stat5a and indicate that the repertoire of potential binding sites for this transcription factor is broader than expected.

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