Theoretical studies on the structural rearrangement of ligand binding pocket in human vitamin D receptor

2010 ◽  
Vol 111 (14) ◽  
pp. 3928-3937
Author(s):  
Jinhu Wang ◽  
Ke Tang ◽  
Qianqian Hou ◽  
Xueli Cheng ◽  
Yongjun Liu ◽  
...  
Keyword(s):  
Vitamin D ◽  
Ligand Binding ◽  
Vitamin D Receptor ◽  
Binding Pocket ◽  
Structural Rearrangement ◽  
Theoretical Studies ◽  
Ligand Binding Pocket

scholarly journals Vitamin D Receptor Agonists Specifically Modulate the Volume of the Ligand-binding Pocket

2006 ◽  
Vol 281 (15) ◽  
pp. 10516-10526 ◽  
Author(s):  
Ferdinand Molnár ◽  
Mikael Peräkylä ◽  
Carsten Carlberg
Keyword(s):  
Vitamin D ◽  
Ligand Binding ◽  
Vitamin D Receptor ◽  
Binding Pocket ◽  
Ligand Binding Pocket ◽  
Receptor Agonists

A New Class of Vitamin D Analogues that Induce Structural Rearrangement of the Ligand-Binding Pocket of the Receptor

2009 ◽  
Vol 52 (5) ◽  
pp. 1438-1449 ◽  
Author(s):  
Yuka Inaba ◽  
Nobuko Yoshimoto ◽  
Yuta Sakamaki ◽  
Makoto Nakabayashi ◽  
Teikichi Ikura ◽  
...  
Keyword(s):  
Vitamin D ◽  
Ligand Binding ◽  
Binding Pocket ◽  
Structural Rearrangement ◽  
Ligand Binding Pocket ◽  
New Class ◽  
Vitamin D Analogues

scholarly journals Ligands with poly-fluorophenyl moieties promote a local structural rearrangement in the Spinach2 and Broccoli aptamers that increases ligand affinities

2021 ◽  
Author(s):  
Sharif Anisuzzaman ◽  
Ivan M Geraskin ◽  
Muslum Ilgu ◽  
Lee Bendickson ◽  
George A Kraus ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Ligand Binding ◽  
Small Molecule ◽  
Binding Pocket ◽  
Structural Rearrangement ◽  
Structural Reorganization ◽  
Ligand Binding Pocket ◽  
Rna Remodeling ◽  
Small Molecule Ligands ◽  
Target Molecules

The interaction of nucleic acids with their molecular targets often involves structural reorganization that may traverse a complex folding landscape. With the more recent recognition that many RNAs, both coding and noncoding, may regulate cellular activities by interacting with target molecules, it becomes increasingly important to understand the means by which nucleic acids interact with their targets and how drugs might be developed that can influence critical folding transitions. We have extensively investigated the interaction of the Spinach2 and Broccoli aptamers with a library of small molecule ligands modified by various extensions from the imido nitrogen of DFHBI (3,5-difluoro-4-hydroxybenzylidene imidazolinone) that reach out from the Spinach2 ligand binding pocket. Studies of the interaction of these compounds with the aptamers revealed that poly-fluorophenyl-modified ligands initiate a slow change in aptamer affinity that takes an extended time (half-life of ~40 min) to achieve. The change in affinity appears to involve an initial disruption of the entrance to the ligand binding pocket followed by a gradual lockdown for which the most likely driving force is an interaction of the gateway adenine with a nearby 2'OH group. These results suggest that poly-fluorophenyl modifications might increase the ability of small molecule drugs to disrupt local structure and promote RNA remodeling.

scholarly journals Suramin Targets the Conserved Ligand-Binding Pocket of Human Raf1 Kinase Inhibitory Protein

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1151
Author(s):  
Chenyun Guo ◽  
Zhihua Wu ◽  
Weiliang Lin ◽  
Hao Xu ◽  
Ting Chang ◽  
...  
Keyword(s):  
Side Effects ◽  
Ligand Binding ◽  
Mapk Pathway ◽  
Regulatory Protein ◽  
Therapeutic Index ◽  
Binding Pocket ◽  
Biological Macromolecules ◽  
Inhibitory Protein ◽  
Ligand Binding Pocket ◽  
Raf1 Kinase

Suramin was initially used to treat African sleeping sickness and has been clinically tested to treat human cancers and HIV infection in the recent years. However, the therapeutic index is low with numerous clinical side-effects, attributed to its diverse interactions with multiple biological macromolecules. Here, we report a novel binding target of suramin, human Raf1 kinase inhibitory protein (hRKIP), which is an important regulatory protein involved in the Ras/Raf1/MEK/ERK (MAPK) signal pathway. Biolayer interference technology showed that suramin had an intermediate affinity for binding hRKIP with a dissociation constant of 23.8 µM. Both nuclear magnetic resonance technology and molecular docking analysis revealed that suramin bound to the conserved ligand-binding pocket of hRKIP, and that residues K113, W173, and Y181 play crucial roles in hRKIP binding suramin. Furthermore, suramin treatment at 160 µM could profoundly increase the ERK phosphorylation level by around 3 times. Our results indicate that suramin binds to hRKIP and prevents hRKIP from binding with hRaf1, thus promoting the MAPK pathway. This work is beneficial to both mechanistically understanding the side-effects of suramin and efficiently improving the clinical applications of suramin.

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