scholarly journals Homology Modeling and Docking Study of Shewanella Like Protein Phosphatase Involved in Development of Ookinetes in Plasmodium

2018 ◽  
Author(s):  
Sandhini Singh ◽  
Ruchi Yadav
Keyword(s):  
Docking Study ◽  
Ligand Interaction ◽  
Docking Method ◽  
Zygote Development ◽  
Drug Designing ◽  
Genes Encoding ◽  
Interaction Scheme ◽  
Effective Role ◽  
Human Infections

ABSTRACTParasites of the genus Plasmodium cause a great deal of morbidity and mortality in worldwide, largely in regions with limited access and indication to the tools necessary to control mosquito populations and to treat human infections of Malaria. Five species of this class of eukaryotic pathogens cause different human disease, with Plasmodium falciparum alone is infecting approximately 500 million people per year and resulting in approximately 1 million deaths. The two genes encoding the Shewanella-like phosphatases of P.falciparum, SHLP-1 and SHLP-2, are conserved among members of Plasmodium family. SHLP is frequently found in asexual blood stages and expressed at all stages of the life cycle of parasite. SHLP deletion results in a reduction in microneme formation, ookinetes (zygote) development and complete ablation of oocyst formation, thereby blocking transmission of parasite.. Structure Modeling of SHLP protein can be helpful in understanding the active site and binding site information and hence can be used for drug designing for therapeutics against malaria. Effective role of Resveratrol is studied against SHLP protein using Docking method to identify protein-ligand interaction scheme and bond formation. Study suggests that resveratrol have strong interaction with SHLP protein and can be used as ligand for drug designing.

scholarly journals Theoretical Evaluation of Bortezomib and Other Boron-Containing Compounds as Inhibitors of SARS-CoV-2 Main Protease

2020 ◽  
Author(s):  
Ivan Ricardo Vega Valdez ◽  
Jose-Martin Santiago-Quintana ◽  
MELVIN ROSALEZ ◽  
Eunice Farfan ◽  
Marvin A. Soriano-Ursua
Keyword(s):  
Crystal Structure ◽  
Binding Site ◽  
Boron Atom ◽  
Docking Study ◽  
Theoretical Evaluation ◽  
Main Protease ◽  
Potent Inhibition ◽  
Drug Designing ◽  
Key Residues

The aim of the present docking study was to explore the putative role of boronic moieties in molecules interacting on the binding site of the SARS-CoV-2 main protease. The methodology was based on the conventional docking procedure by means of AutoDock software by assaying boron-free and boron-containing compounds on the recent reported crystal structure of SARS-CoV-2 main protease (PDB code: 6LU7). The most of tested compounds share contact with key residues and poses on the cleavage pocket. Those compounds with a boron atom in its structure often were estimated with higher affinity than boron-free analogues. Interactions and affinity of boron-containing peptidomimetics on the binding site let us to propose the potent inhibition of these compounds on targeted protease. These advances may be relevant for drug designing, but also to suggest the testing of available boron-containing drugs in patients with severe symptoms of COVID19 infection.

scholarly journals Studi Penambatan Molekul Senyawa Curcuma longa pada Bakteri Resisten Carbapenem Acinetobacter baumanii dengan Metode In Silico

2021 ◽  
Vol 3 (1) ◽  
pp. 124-130
Author(s):  
Nabila Shafa Athharani ◽  
Nugraha Sutadipura ◽  
Yuli Susanti
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Raw Materials ◽  
Curcuma Longa ◽  
Docking Study ◽  
The Body ◽  
Molecular Docking Study ◽  
Acinetobacter Baumanii ◽  
Docking Method

Penemuan berbagai senyawa obat baru dari berbagai proses penelitian yang semakin memperjelas peran penting studi komputasi sebagai dasar awal untuk menemukan sumber bahan baku obat baik dari alam maupun sintetis. Infeksi nosokomial dapat disebabkan oleh bakteri, virus atau patogen lain di rumah sakit, dan ditularkan melalui peralatan di rumah sakit. Salah satu bakteri yang paling sering menyebabkan infeksi adalah Acinetobacter baumanii bakteri tersebut dapat membangun resistensi dalam tubuh. Metode penelitian ini dilakukan secara in silico dengan metode molecular docking dengan melihat penambatan molekul senyawa yang dimilikinya. Hasil penelitian menunjukkan bahwa senyawa yang diuji terhadap target reseptor yaitu Acinetobacter baumanii memiliki kemampuan sebagai antibakteri, terlihat dari ikatan afinitas yang diperoleh dari sekitar -7,7 kkal/mol hingga -8,1 kkal/mol. Kesimpulannya, kunyit dapat digunakan sebagai kandidat untuk mencegah Acinetobacter baumanii menjadi resisten. Molecular Docking Study of Curcuma Longa Compounds on Bacteria Resistant Carbapenem Acinetobacter Baumanii with in Silico MethodThe discovery of various new medicinal compounds from various research processes that further clarify the important role of computational studies as the initial basis for finding sources of medicinal raw materials both from natural and synthetic. Nosocomial infections can be caused by bacteria, viruses or other pathogens in the hospital and transmitted through equipment in the hospital. One of the bacteria that most often causes infection is Acinetobacter baumanii where these bacteria can build up resistance in the body. Method  of  this research is carried out in silico with the molecular docking method by looking at the docking of its compound molecules. The results showed that of the compounds tested against the receptor target, Acinetobacter Baumanii, had the ability as antibacterial, seen from the affinity bonds obtained from around -7.7 kcal/mol to -8.1 kcal/mol.  Conclusion is turmeric can be used as a candidate to prevent Acinetobacter baumanii from becoming resistance.

scholarly journals Theoretical Evaluation of Bortezomib and Other Boron-Containing Compounds as Inhibitors of SARS-CoV-2 Main Protease

2020 ◽  
Author(s):  
Ivan Ricardo Vega Valdez ◽  
Jose-Martin Santiago-Quintana ◽  
MELVIN ROSALEZ ◽  
Eunice Farfan ◽  
Marvin A. Soriano-Ursua
Keyword(s):  
Crystal Structure ◽  
Binding Site ◽  
Boron Atom ◽  
Docking Study ◽  
Theoretical Evaluation ◽  
Main Protease ◽  
Potent Inhibition ◽  
Drug Designing ◽  
Key Residues

The aim of the present docking study was to explore the putative role of boronic moieties in molecules interacting on the binding site of the SARS-CoV-2 main protease. The methodology was based on the conventional docking procedure by means of AutoDock software by assaying boron-free and boron-containing compounds on the recent reported crystal structure of SARS-CoV-2 main protease (PDB code: 6LU7). The most of tested compounds share contact with key residues and poses on the cleavage pocket. Those compounds with a boron atom in its structure often were estimated with higher affinity than boron-free analogues. Interactions and affinity of boron-containing peptidomimetics on the binding site let us to propose the potent inhibition of these compounds on targeted protease. These advances may be relevant for drug designing, but also to suggest the testing of available boron-containing drugs in patients with severe symptoms of COVID19 infection.

scholarly journals Characterization of the human and mouse genes encoding the tuberoinfundibular peptide of 39 residues, a ligand of the parathyroid hormone receptor family

2002 ◽  
Vol 174 (1) ◽  
pp. 95-102 ◽  
Author(s):  
IA Hansen ◽  
O Jakob ◽  
S Wortmann ◽  
T Arzberger ◽  
B Allolio ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Receptor Activation ◽  
Human Organism ◽  
Ligand Interaction ◽  
Transfected Cells ◽  
Genes Encoding ◽  
Tuberoinfundibular Peptide ◽  
Human And Mouse ◽  
Receptor Family

The polypeptide TIP39 (tuberoinfundibular peptide of 39 residues) is a potent activator of the parathyroid hormone (PTH)-2 receptor (P2R) and an antagonist of the PTH-1 receptor (P1R). To clarify its possible physiological function(s), we studied its interaction with the human P1R and P2R and examined the expression of TIP39 in man and mouse. To find out possible sites of this ligand interaction in the organism, we identified the genes encoding the TIP39 protein precursors of Homo sapiens and Mus musculus in the databases of the human and mouse genome projects respectively. We then obtained the full-length cDNAs of both species by RACE-PCR. The deduced TIP39 preprohormones consist of an N-terminal 30 amino acid (aa) signal peptide followed by a 29 aa TIP39 precursor-related peptide, an Arg-Arg processing site, and the actual 39 aa TIP39 sequence. The first 23 aa of the actual TIP39 sequence, thought to contain the P2R receptor activation site, are identical in man and mouse and thus phylogenetically conserved. By contrast, the 16 aa C-terminal portion showed a higher degree of diversity (75% aa identity). By using RT-PCR, TIP39 was found to be highly expressed in human central nervous system tissues, trachea, fetal liver, and, to a lesser degree, in human heart and kidney. Using in situ hybridization, TIP39 mRNA expression was revealed in various areas of the mouse brain. In a homologous human cell model using human embryonic kidney 293 cells stably transfected with human P1R and P2R, human TIP39 did bind to P1R with moderate affinity (IC(50) approximately 10(-7)-10(-6 )M), but showed higher affinity binding to P2R (IC(50) approximately 10(-8)M), comparable to the affinity of human N-terminal PTH (hPTH(1-34)) to this receptor. In P2R-transfected cells, the cAMP pathway was activated more efficiently ( approximately 10-fold) by TIP39 as a ligand compared to hPTH(1-34). In P1R-transfected cells, only hPTH(1-34) but not TIP39 was able to elicit a cAMP response, but TIP39 was able to directly antagonize the cAMP-stimulating effect of hPTH(1-34) on this receptor. In conclusion, we could show a possible function of TIP39 for the human organism as a potent activator of P2R (e.g. in brain) as well as an antagonist of the action of PTH and/or PTH-related protein on P1R (e.g. in bone and kidney). The physiological role of TIP39 in calcium metabolism with regard to these actions remains to be determined. The tools developed in this work will allow us to investigate the possible role of TIP39 as a locally or systemically secreted ligand modulating the function of the PTH receptor family.

DNA methylation in satellite repeats disorders

2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Repetitive Dna ◽  
Dna Sequences ◽  
Satellite Repeats ◽  
Tremendous Progress ◽  
Genes Encoding ◽  
Dna Elements ◽  
Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

Reforming the Role of the African Commission on Human and Peoples’ Rights in Advancing Democratic Principles and Human Rights in African Countries: An Examination Using the Lens of Swaziland/ eSwatini

2019 ◽  
Vol 34 (2) ◽  
Author(s):  
Jeremy Sarkin
Keyword(s):  
Human Rights ◽  
African Countries ◽  
Individual Country ◽  
The Status ◽  
Effective Role ◽  
Limited Compliance ◽  
Fact Finding ◽  
Democratic Principles ◽  
African Commission

This article explores the role of the African Commission on Human and Peoples’ Rights and the role it plays regarding human rights in individual country situations in Africa. It specifically examines the extent to which it has been able to advance a human rights agenda in countries with long-standing human rights problems. The article uses Swaziland/ eSwatini as a lens to examine the matter, because of the longstanding problems that exist in that country. This is done to indicate how the institution works over time on a country’s human rights problems. The article examines a range of institutional structural matters to establish how these issues affect the role of the Commission in its work. The article examines the way in which the Commission uses its various tools, including its communications, the state reporting processes, fact-finding visits, and resolutions, to determine whether those tools are being used effectively. The article examines how the Commission’s processes issues also affect it work. Issues examined negatively affecting the Commission are examined, including problems with the status of its resolutions and communications, limited compliance with its outcomes, and inadequate state cooperation. Reforms necessary to enhance to role and functions of the Commission are surveyed to determine how the institution could become more effective. The African Union’s (AU|) Kagame Report on AU reform is briefly reviewed to examine the limited view and focus of AU reform processes and why AU reform ought to focus on enhancing human rights compliance. The article makes various suggestions on necessary institutional reforms but also as far as the African Commission’s procedures and methods of work to allow it to have a far more effective role in the promotion and protection of human rights on the continent. It is noted that political will by the AU and African states is the largest obstacle to giving the Commission the necessary independence, support and assistance that it needs to play the role in Africa that it should.

Microbial Bioconversion: A Regio-specific Method for Novel Drug Design and Toxicological Study of Metabolites

2019 ◽  
Vol 20 (14) ◽  
pp. 1156-1162
Author(s):  
Maria Yousuf ◽  
Waqas Jamil ◽  
Khayala Mammadova
Keyword(s):  
Microbial Transformation ◽  
Specific Method ◽  
Reaction Conditions ◽  
Small Organic Molecules ◽  
Toxicological Studies ◽  
Drug Designing ◽  
Transformation Methods ◽  
Novel Drug

The methods of chemical structural alteration of small organic molecules by using microbes (fungi, bacteria, yeast, etc.) are gaining tremendous attention to obtain structurally novel and therapeutically potential leads. The regiospecific mild environmental friendly reaction conditions with the ability of novel chemical structural modification in compounds categorize this technique; a distinguished and unique way to obtain medicinally important drugs and their in vivo mimic metabolites with costeffective and timely manner. This review article shortly addresses the immense pharmaceutical importance of microbial transformation methods in drug designing and development as well as the role of CYP450 enzymes in fungi to obtain in vivo drug metabolites for toxicological studies.

Towards further Understanding the Structural Requirements of Combretastatin- like Chalcones as Inhibitors of Microtubule Polymerization

2020 ◽  
Vol 16 (2) ◽  
pp. 155-166
Author(s):  
Naveen Dhingra ◽  
Anand Kar ◽  
Rajesh Sharma
Keyword(s):  
Three Dimensional ◽  
3D Qsar ◽  
Docking Study ◽  
Structure Activity Relationship ◽  
Docking Studies ◽  
Activity Relationship ◽  
Structural Requirement ◽  
Ligand Interaction ◽  
Microtubule Polymerization ◽  
Structure Activity

Background: Microtubules are dynamic filamentous cytoskeletal structures which play several key roles in cell proliferation and trafficking. They are supposed to contribute in the development of important therapeutic targeting tumor cells. Chalcones are important group of natural compounds abundantly found in fruits & vegetables that are known to possess anticancer activity. We have used QSAR and docking studies to understand the structural requirement of chalcones for understanding the mechanism of microtubule polymerization inhibition. Methods: Three dimensional (3D) QSAR (CoMFA and CoMSIA), pharmacophore mapping and molecular docking studies were performed for the generation of structure activity relationship of combretastatin-like chalcones through statistical models and contour maps. Results: Structure activity relationship revealed that substitution of electrostatic, steric and donor groups may enhance the biological activity of compounds as inhibitors of microtubule polymerization. From the docking study, it was clear that compounds bind at the active site of tubulin protein. Conclusion: The given strategies of modelling could be an encouraging way for designing more potent compounds as well as for the elucidation of protein-ligand interaction.

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