scholarly journals Molecular Modeling of a Tandem Two Pore Domain Potassium Channel Reveals a Putative Binding Site for General Anesthetics

2014 ◽  
Vol 5 (12) ◽  
pp. 1246-1252 ◽  
Author(s):  
Edward J. Bertaccini ◽  
Robert Dickinson ◽  
James R. Trudell ◽  
Nicholas P. Franks
Keyword(s):  
Molecular Modeling ◽  
Potassium Channel ◽  
Binding Site ◽  
General Anesthetics ◽  
Pore Domain ◽  
Putative Binding Site

Synthesis, Anti-proliferative Evaluation, and Molecular Docking Studies of 3-(alkylthio)-5,6-diaryl-1,2,4-triazines as Tubulin Polymerization Inhibitors

2019 ◽  
Vol 16 (11) ◽  
pp. 1194-1201 ◽  
Author(s):  
Farhad Saravani ◽  
Ebrahim Saeedian Moghadam ◽  
Hafezeh Salehabadi ◽  
Seyednasser Ostad ◽  
Morteza Pirali Hamedani ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Cytotoxic Activity ◽  
Binding Site ◽  
Cell Line ◽  
Cell Lines ◽  
Tubulin Polymerization ◽  
Adenocarcinoma Cell Line ◽  
Adenocarcinoma Cell ◽  
Colchicine Binding Site ◽  
Anti Cancer

Background: The role of microtubules in cell division and signaling, intercellular transport, and mitosis has been well known. Hence, they have been targeted for several anti-cancer drugs. Methods: A series of 3-(alkylthio)-5,6-diphenyl-1,2,4-triazines were prepared and evaluated for their cytotoxic activities in vitro against three human cancer cell lines; human colon carcinoma cells HT-29, human breast adenocarcinoma cell line MCF-7, human Caucasian gastric adenocarcinoma cell line AGS as well as fibroblast cell line NIH-3T3 by MTT assay. Docking simulation was performed to insert these compounds into the crystal structure of tubulin at the colchicine binding site to determine a probable binding model. Compound 5d as the most active compound was selected for studying of microtubule disruption. Results: Compound 5d showed potent cytotoxic activity against all cell lines. The molecular modeling study revealed that some derivatives of triazine strongly bind to colchicine binding site. The tubulin polymerization assay kit showed that the cytotoxic activity of 5d may be related to inhibition of tubulin polymerization. Conclusion: The cytotoxicity and molecular modeling study of the synthesized compounds with their inhibition activity in tubulin polymerization demonstrate the potential of triazine derivatives for development of new anti-cancer agents.

scholarly journals Bioinformatic Analysis of the Nicotinamide Binding Site in Poly(ADP-Ribose) Polymerase Family Proteins

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1201
Author(s):  
Garri Manasaryan ◽  
Dmitry Suplatov ◽  
Sergey Pushkarev ◽  
Viktor Drobot ◽  
Alexander Kuimov ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Cancer Therapy ◽  
Adverse Effects ◽  
Binding Site ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Bioinformatic Analysis ◽  
Parp Inhibitors ◽  
Functional Region ◽  
D Loop

The PARP family consists of 17 members with diverse functions, including those related to cancer cells’ viability. Several PARP inhibitors are of great interest as innovative anticancer drugs, but they have low selectivity towards distinct PARP family members and exert serious adverse effects. We describe a family-wide study of the nicotinamide (NA) binding site, an important functional region in the PARP structure, using comparative bioinformatic analysis and molecular modeling. Mutations in the NA site and D-loop mobility around the NA site were identified as factors that can guide the design of selective PARP inhibitors. Our findings are of particular importance for the development of novel tankyrase (PARPs 5a and 5b) inhibitors for cancer therapy.

scholarly journals TWIK-2, a new weak inward rectifying member of the tandem pore domain potassium channel family.

1999 ◽  
Vol 274 (34) ◽  
pp. 24440
Author(s):  
Raymond A. Chavez ◽  
Andrew T. Gray ◽  
Byron B. Zhao ◽  
Christoph H. Kindler ◽  
Matthew J. Mazurek ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Pore Domain

Discovery of a Pharmacologically Active Antagonist of the Two-Pore-Domain Potassium Channel K2P9.1 (TASK-3)

ChemMedChem ◽  
2011 ◽  
Vol 7 (1) ◽  
pp. 123-133 ◽  
Author(s):  
Craig A. Coburn ◽  
Yunfu Luo ◽  
Mingxiang Cui ◽  
Jiabing Wang ◽  
Richard Soll ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Pharmacologically Active ◽  
Pore Domain

scholarly journals Characterizing the Fatty Acid Binding Site in the Cavity of Potassium Channel KcsA

Biochemistry ◽  
2012 ◽  
Vol 51 (40) ◽  
pp. 7996-8002 ◽  
Author(s):  
Natalie Smithers ◽  
Juan H. Bolivar ◽  
Anthony G. Lee ◽  
J. Malcolm East
Keyword(s):  
Fatty Acid ◽  
Potassium Channel ◽  
Binding Site ◽  
Fatty Acid Binding ◽  
Potassium Channel Kcsa ◽  
Fatty Acid Binding Site

Exploring the Hexokinase Glucose Binding Site Through Correlation Analysis and Molecular Modeling of Glucosamine Inhibitors

1993 ◽  
Vol 6 (4) ◽  
pp. 271-282 ◽  
Author(s):  
Eugene A. Coats ◽  
Kenneth A. Skau ◽  
Carol A Caperelli ◽  
David Solomacha
Keyword(s):  
Molecular Modeling ◽  
Correlation Analysis ◽  
Binding Site ◽  
Glucose Binding

scholarly journals Identifying ligand-binding specificity of the oligopeptide receptor OppA from Bifidobacterium longum KACC91563 by Structure-based molecular modeling

2020 ◽  
Author(s):  
Han-Ha Chai ◽  
Young Ran Kim ◽  
Jun-Sang Ham ◽  
Tae-Hun Kim ◽  
Dajeong Lim
Keyword(s):  
Molecular Modeling ◽  
Structure Function ◽  
Binding Site ◽  
Bifidobacterium Longum ◽  
Peptide Binding ◽  
Binding Pocket ◽  
Host Organism ◽  
Specialized Structure ◽  
Function Relationship ◽  
The Relationship

Abstract Background: The OppA receptor as a ATP-binding cassette (ABC) transporter plays key roles in protecting host organism and transport nutrients across the intestine by the oligopeptide transporter from symbiotic bacteria directs maturation of the host immune system. Among lactic acid bacteria, Bifidobacterium longum KACC91563, isolated from fecal samples of healthy Korean neonates, has the capability to alleviate food allergy effects. The extracellular OppA receptor from gram-positive Bifidobacterium longum KACC91563 translocate nutrients-peptides from the outside environment of intestinal tract to the inside of the symbiotic cell, as a peptide importer. Hence, it was attempting to explicate the relationship between the substrate’s specificity from the OppA importer and the probiotic effects of B. logum KACC91563 in the host intestine. The probiotic effects of B. logum KACC91563 were attributed to the enhancement of the epithelial barrier by several different strain sepcific ways to prevent the strong adhesion of pathogens. The specialized structure-function relationship from the OppA importer could provide the abstract of substrate specificity into unique immunological properties of that the host organism.Results: In the study, we characterized the extracellular OppA importer from B. longum KACC91563 of intestinal microbiome by various protein structure-based modelings in silico. Structural characterization by conserved 5 patches and 4 functional motifs from specific trace residues of the OppA importer. The hydrate surface of the binding site had been decipted by specific trace residues of the OppA that trace residues of Thr58, Lys185, Trp443, and Tyr447, which were characterized in highly exposed hydrophobic binding pocket by its aggregation prones. Therefore, the spatial aggregation propensity in the binding site of the extracellular OppA importer plays a vital role in the specific interaction determinant for peptide binding. In addition, alanine mutation energy values allowed for the virtual determination of the relationships between the energy effects of the peptide binding site mutation on the transporter structural stability, the peptide binding affinity, and the transporter-related peptide substrate selectivity from OppA importer. In particular, distinctive seven pharmacophoric features comprised of two H-bonding donor(P1), three H-bonding acceptor(P8), and two hydrophobic points (P5 and P8) matched the the OppA receptor-peptide ligand interactions within their binding pocket structure. There are distinct interactions to fix the positions of the N(P1) and C(P8) termini of the complex of OppA-peptide from B. longum KACC91563 such as side chain-specific interactions with the OppA, compared to that of the Lactococcus latis (L. lactics) OppA.Conclusions: The specialized structure-function relationship from the OppA import could provide the abstract of substrate specificity into unique immunological properties of the host organism by stucutre-based molecular modeling. In the current study, we attempted explication of the relationship between the substrate’s specificity from the OppA importer and the probiotic effects of B. longum KACC91563 in the host intestine based on the structure-function perspectives of the OppA importer. Moreover, functional characterization of solute-binding proteins (such as 15 cell wall proteins and 20 extracellular proteins) on the B. longum KACC91563 genome will lead to insight of key switch for substate’s metabolism into reprogramming immune responses in the host intestine.

Cloxyquin (5-chloroquinolin-8-ol) is an activator of the two-pore domain potassium channel TRESK

2013 ◽  
Vol 441 (2) ◽  
pp. 463-468 ◽  
Author(s):  
Paul D. Wright ◽  
Gregory Weir ◽  
Jamie Cartland ◽  
David Tickle ◽  
Catherine Kettleborough ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Pore Domain
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