ChemInform Abstract: Synthesis and Axial-Ligand Binding of Zinc Complexes of Amphiphilic Porphyrins Containing a Hydrophobic Binding Pocket

ChemInform ◽  
2010 ◽  
Vol 28 (49) ◽  
pp. no-no
Author(s):  
H. IMAI ◽  
H. MUNAKATA ◽  
A. TAKAHASHI ◽  
S. NAKAGAWA ◽  
Y. UEMORI
Keyword(s):  
Ligand Binding ◽  
Binding Pocket ◽  
Axial Ligand ◽  
Zinc Complexes ◽  
Hydrophobic Binding

Synthesis and Axial-Ligand Binding of Zinc Complexes of Amphiphilic Porphyrins Containing a Hydrophobic Binding Pocket

1997 ◽  
Vol 26 (8) ◽  
pp. 819-820 ◽  
Author(s):  
Hiroyasu Imai ◽  
Hiroki Munakata ◽  
Atsuko Takahashi ◽  
Shigeo Nakagawa ◽  
Yoshio Uemori
Keyword(s):  
Ligand Binding ◽  
Binding Pocket ◽  
Axial Ligand ◽  
Zinc Complexes ◽  
Hydrophobic Binding

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.

The determination of axial ligand binding constants for iron porphyrins by cyclic voltammetry

1991 ◽  
Vol 68 (4) ◽  
pp. 337 ◽  
Author(s):  
David K. Geiger ◽  
Edmund J. Paviak ◽  
Lawrence T. Kass
Keyword(s):  
Cyclic Voltammetry ◽  
Ligand Binding ◽  
Binding Constants ◽  
Axial Ligand ◽  
Iron Porphyrins

scholarly journals Structure of the Lifeact–F-actin complex

PLoS Biology ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. e3000925 ◽  
Author(s):  
Alexander Belyy ◽  
Felipe Merino ◽  
Oleg Sitsel ◽  
Stefan Raunser
Keyword(s):  
Hypervariable Region ◽  
Binding Pocket ◽  
Actin Binding ◽  
Filamentous Actin ◽  
Activity Measurements ◽  
High Resolution Structure ◽  
D Loop ◽  
Hydrophobic Binding

Lifeact is a short actin-binding peptide that is used to visualize filamentous actin (F-actin) structures in live eukaryotic cells using fluorescence microscopy. However, this popular probe has been shown to alter cellular morphology by affecting the structure of the cytoskeleton. The molecular basis for such artefacts is poorly understood. Here, we determined the high-resolution structure of the Lifeact–F-actin complex using electron cryo-microscopy (cryo-EM). The structure reveals that Lifeact interacts with a hydrophobic binding pocket on F-actin and stretches over 2 adjacent actin subunits, stabilizing the DNase I-binding loop (D-loop) of actin in the closed conformation. Interestingly, the hydrophobic binding site is also used by actin-binding proteins, such as cofilin and myosin and actin-binding toxins, such as the hypervariable region of TccC3 (TccC3HVR) from Photorhabdus luminescens and ExoY from Pseudomonas aeruginosa. In vitro binding assays and activity measurements demonstrate that Lifeact indeed competes with these proteins, providing an explanation for the altering effects of Lifeact on cell morphology in vivo. Finally, we demonstrate that the affinity of Lifeact to F-actin can be increased by introducing mutations into the peptide, laying the foundation for designing improved actin probes for live cell imaging.

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.

Ligand binding pocket function of Drosophila USP is necessary for metamorphosis

2013 ◽  
Vol 182 ◽  
pp. 73-82 ◽  
Author(s):  
Grace Jones ◽  
Peter Teal ◽  
Vincent C. Henrich ◽  
Anna Krzywonos ◽  
Agnes Sapa ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Pocket ◽  
Ligand Binding Pocket

Subcellular localization defects characterize ribose-binding mutant proteins with new ligand properties in Escherichia coli

2021 ◽  
Author(s):  
Diogo Tavares ◽  
Jan R. van der Meer
Keyword(s):  
Escherichia Coli ◽  
Subcellular Localization ◽  
Ligand Binding ◽  
Binding Proteins ◽  
Binding Protein ◽  
Binding Pocket ◽  
Binding Properties ◽  
General Properties ◽  
Periplasmic Binding Proteins ◽  
Ribose Binding Protein

Periplasmic-binding proteins have been previously proclaimed as a general scaffold to design sensor proteins with new recognition specificities for non-natural compounds. Such proteins can be integrated in bacterial bioreporter chassis with hybrid chemoreceptors to produce a concentration-dependent signal after ligand binding to the sensor cell. However, computationally designed new ligand-binding properties ignore the more general properties of periplasmic binding proteins, such as their periplasmic translocation, dynamic transition of open and closed forms, and interactions with membrane receptors. In order to better understand the roles of such general properties in periplasmic signaling behaviour, we study here the subcellular localization of ribose-binding protein (RbsB) in Escherichia coli in comparison to a recently evolved set of mutants designed to bind 1,3-cyclohexanediol. As proxies for localization we calibrate and deploy C-terminal end mCherry fluorescent protein fusions. Whereas RbsB-mCherry coherently localized to the periplasmic space and accumulated in (periplasmic) polar regions depending on chemoreceptor availability, mutant RbsB-mCherry expression resulted in high fluorescence cell-to-cell variability. This resulted in higher proportions of cells devoid of clear polar foci and of cells with multiple fluorescent foci elsewhere, suggesting poorer translocation, periplasmic autoaggregation and mislocalization. Analysis of RbsB mutants and mutant libraries at different stages of directed evolution suggested overall improvement to more RbsB-wild-type-like characteristics, which was corroborated by structure predictions. Our results show that defects in periplasmic localization of mutant RbsB proteins partly explains their poor sensing performance. Future efforts should be directed to predicting or selecting secondary mutations outside computationally designed binding pockets that take folding, translocation and receptor-interactions into account. Importance Biosensor engineering relies on transcription factors or signaling proteins to provide the actual sensory functions for the target chemicals. Since for many compounds there are no natural sensory proteins, there is a general interest in methods that could unlock routes to obtaining new ligand-binding properties. Bacterial periplasmic-binding proteins (PBPs) form an interesting family of proteins to explore to this purpose, because there is a large natural variety suggesting evolutionary trajectories to bind new ligands. PBPs are conserved and amenable to accurate computational binding pocket predictions. However, studying ribose-binding protein in Escherichia coli we discovered that designed variants have defects in their proper localization in the cell, which can impair appropriate sensor signaling. This indicates that functional sensing capacity of PBPs cannot be obtained solely through computational design of the ligand-binding pocket, but must take other properties of the protein into account, which are currently very difficult to predict.

Sign in / Sign up

Export Citation Format

Share Document