In silico approach to ascertain the calcium dependent role of Plasmodium falciparum SERA5

Met die toenemende voorkoms van weerstandige Plasmodium stamme het die beheer van malaria-voorkoms en -mortaliteit weer op die voorgrond getree. Nuwe teikens en antimalariamiddels wat effektief is teen weerstandige malaria-parasiete word dus dringend benodig. Kalsium-afhanklike proteïenkinases (calcium dependent protein kinases – CDPKs) is betrokke by die beheer van ’n aantal biologiese prosesse in die malaria-parasiet, Plasmodium falciparum, met CDPK4 die belangrikste ensiem in hierdie klas. In hierdie studie is die struktuur van PfCDPK4 gebruik as templaat vir die soeke na nuwe malariamiddels. Die PfCDPK4 modelstruktuur is deur middel van homologiemodellering gegenereer en die stereochemiese kwaliteit gevalideer. Die molekulêre modelleringbenadering deur middel van in silico sifting teen die teiken-molekuul PfCDPK4 het ’n beskeie biblioteek van 20 000 chemiese verbindings ingesluit, asook ’n aantal aktiewe natuurprodukte en kliniesgoedgekeurde kinase-inhibeerders. In silico sifting van die Biofocus biblioteek teen PfCDPK4 het 26 verbindings opgelewer; in vitro sifting het bevestig dat drie van hierdie verbindings matig aktief is teen Plasmodium falciparum NF54, met persentasie inhibisie tussen 42% en 47%.

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The emerging role of calcium-dependent exocytosis in ATP release from nonexcitable cells

10.36866/pn.60.21 ◽

2005 ◽

pp. 21-22 ◽

Cited By ~ 1

Author(s):

Ryszard Grygorczyk ◽

Francis Boudreault

Keyword(s):

Atp Release ◽

Calcium Dependent

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The Redox Systems of Plasmodium falciparum and Plasmodium vivax: Comparison, In silico Analyses and Inhibitor Studies

Current Medicinal Chemistry ◽

10.2174/0929867321666131201144612 ◽

2014 ◽

Vol 21 (15) ◽

pp. 1728-1756 ◽

Cited By ~ 16

Author(s):

F. Mohring ◽

J. Pretzel ◽

E. Jortzik ◽

K. Becker

Keyword(s):

Plasmodium Falciparum ◽

Plasmodium Vivax ◽

In Silico ◽

Redox Systems ◽

In Silico Analyses

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Effect of Annexins Translocated in Extracellular Vesicles on Tumorigenesis

Current Molecular Medicine ◽

10.2174/1566524020666200825163512 ◽

2020 ◽

Vol 20 ◽

Author(s):

Qionghui Wu ◽

Haidong Wei ◽

Wenbo Meng ◽

Xiaodong Xie ◽

Zhenchang Zhang ◽

...

Keyword(s):

Tumor Cells ◽

Extracellular Vesicles ◽

Immune Cell ◽

Epithelial Mesenchymal Transition ◽

Main Role ◽

Tumor Cell Adhesion ◽

Mesenchymal Transition ◽

Calcium Dependent ◽

Tumor Neovascularization

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.

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Apicoplast Import Protein Tic20 A Promising Therapeutic Molecular Target for Plasmodium falciparum: An In Silico Approach for Therapeutic Intervention

Infectious Disorders - Drug Targets ◽

10.2174/1871526517666170606113133 ◽

2017 ◽

Vol 17 (3) ◽

Author(s):

Ravi C P. K. Srimath-Tirumala-Peddinti ◽

Sandeep S. Kusuma ◽

Deepthi Nammi ◽

Nageswara R.R. Neelapu

Keyword(s):

Plasmodium Falciparum ◽

Therapeutic Intervention ◽

In Silico ◽

Molecular Target

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MATRIX – In silico and in vitro Models of Angiogenesis: unravelling the role of the extracellular matrix – ERC

Impact ◽

10.21820/23987073.2017.4.45 ◽

2017 ◽

Vol 2017 (4) ◽

pp. 45-47

Author(s):

Hans Van Ooosterwyck

Keyword(s):

Extracellular Matrix ◽

In Silico ◽

In Vitro Models

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Intracellular Na+ Modulates Pacemaking Activity in Murine Sinoatrial Node Myocytes: An In Silico Analysis

International Journal of Molecular Sciences ◽

10.3390/ijms22115645 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5645

Author(s):

Stefano Morotti ◽

Haibo Ni ◽

Colin H. Peters ◽

Christian Rickert ◽

Ameneh Asgari-Targhi ◽

...

Keyword(s):

Heart Failure ◽

Membrane Potential ◽

In Silico ◽

Sinoatrial Node ◽

In Silico Analysis ◽

Ankyrin B ◽

Deficient Mice ◽

Silico Analysis ◽

Bursting Activity

Background: The mechanisms underlying dysfunction in the sinoatrial node (SAN), the heart’s primary pacemaker, are incompletely understood. Electrical and Ca2+-handling remodeling have been implicated in SAN dysfunction associated with heart failure, aging, and diabetes. Cardiomyocyte [Na+]i is also elevated in these diseases, where it contributes to arrhythmogenesis. Here, we sought to investigate the largely unexplored role of Na+ homeostasis in SAN pacemaking and test whether [Na+]i dysregulation may contribute to SAN dysfunction. Methods: We developed a dataset-specific computational model of the murine SAN myocyte and simulated alterations in the major processes of Na+ entry (Na+/Ca2+ exchanger, NCX) and removal (Na+/K+ ATPase, NKA). Results: We found that changes in intracellular Na+ homeostatic processes dynamically regulate SAN electrophysiology. Mild reductions in NKA and NCX function increase myocyte firing rate, whereas a stronger reduction causes bursting activity and loss of automaticity. These pathologic phenotypes mimic those observed experimentally in NCX- and ankyrin-B-deficient mice due to altered feedback between the Ca2+ and membrane potential clocks underlying SAN firing. Conclusions: Our study generates new testable predictions and insight linking Na+ homeostasis to Ca2+ handling and membrane potential dynamics in SAN myocytes that may advance our understanding of SAN (dys)function.

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A CACNA1A variant associated with trigeminal neuralgia alters the gating of Cav2.1 channels

Molecular Brain ◽

10.1186/s13041-020-00725-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Eder Gambeta ◽

Maria A. Gandini ◽

Ivana A. Souza ◽

Laurent Ferron ◽

Gerald W. Zamponi

Keyword(s):

Trigeminal Neuralgia ◽

Missense Mutation ◽

Neurotransmitter Release ◽

Trigeminal System ◽

Wild Type ◽

Calcium Dependent ◽

Whole Cell Patch Clamp ◽

C Terminus ◽

Dependent Inactivation

AbstractA novel missense mutation in the CACNA1A gene that encodes the pore forming α1 subunit of the CaV2.1 voltage-gated calcium channel was identified in a patient with trigeminal neuralgia. This mutation leads to a substitution of proline 2455 by histidine (P2455H) in the distal C-terminus region of the channel. Due to the well characterized role of this channel in neurotransmitter release, our aim was to characterize the biophysical properties of the P2455H variant in heterologously expressed CaV2.1 channels. Whole-cell patch clamp recordings of wild type and mutant CaV2.1 channels expressed in tsA-201 cells reveal that the mutation mediates a depolarizing shift in the voltage-dependence of activation and inactivation. Moreover, the P2455H mutant strongly reduced calcium-dependent inactivation of the channel that is consistent with an overall gain of function. Hence, the P2455H CaV2.1 missense mutation alters the gating properties of the channel, suggesting that associated changes in CaV2.1-dependent synaptic communication in the trigeminal system may contribute to the development of trigeminal neuralgia.

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