scholarly journals In Silico Studies on Development of Novel Virostatic Agents against Bluetongue Virus

ISRN Virology ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Pandrangi Anupama
Keyword(s):  
Bluetongue Virus ◽  
Core Protein ◽  
Critical Role ◽  
Docking Studies ◽  
Site Specific ◽  
The Core ◽  
In Silico Studies ◽  
Vp7 Protein ◽  
Major Core Protein

The core of BTV is organized into three concentric structures of which VP7 protein forms the major core protein. The subcore consists of VP3 protein and the innermost part of the core is made of three minor proteins: VP1, VP4, and VP6. Earlier it was reported that core-like particles (CLPs) composed of viral VP7 and VP3 proteins were produced in order to study role of VP7 protein in intermolecular interactions in the BTV assembly process. Site specific mutational studies revealed that substitution of the single lysine residue of VP7 (Lys-255) by leucine abrogated CLP formation, indicating a critical role for this lysine. In the present study, homology modeling, mutagenesis, and docking studies were carried out in order to design potent leads in modulation of VP7 protein in abrogating CLP formation.

scholarly journals RGD Tripeptide of Bluetongue Virus VP7 Protein Is Responsible for Core Attachment to Culicoides Cells

2001 ◽  
Vol 75 (8) ◽  
pp. 3937-3947 ◽  
Author(s):  
Boon-Huan Tan ◽  
Emma Nason ◽  
Norbert Staeuber ◽  
Wenrong Jiang ◽  
Katherine Monastryrskaya ◽  
...  
Keyword(s):  
Bluetongue Virus ◽  
Mammalian Cells ◽  
Inner Core ◽  
Core Protein ◽  
Binding Activity ◽  
Cell Binding ◽  
Rgd Motif ◽  
The Core ◽  
Vp7 Protein

ABSTRACT Bluetongue virus (BTV) is an arthropod-borne virus transmitted byCulicoides species to vertebrate hosts. The double-capsid virion is infectious for Culicoides vector and mammalian cells, while the inner core is infectious for onlyCulicoides-derived cells. The recently determined crystal structure of the BTV core has revealed an accessible RGD motif between amino acids 168 to 170 of the outer core protein VP7, whose structure and position would be consistent with a role in cell entry. To delineate the biological role of the RGD sequence within VP7, we have introduced point mutations in the RGD tripeptide and generated three recombinant baculoviruses, each expressing a mutant derivative of VP7 (VP7-AGD, VP7-ADL, and VP7-AGQ). Each expressed mutant protein was purified, and the oligomeric nature and secondary structure of each was compared with those of the wild-type (wt) VP7 molecule. Each mutant VP7 protein was used to generate empty core-like particles (CLPs) and were shown to be biochemically and morphologically identical to those of wt CLPs. However, when mutant CLPs were used in an in vitro cell binding assay, each showed reduced binding to Culicoides cells compared to wt CLPs. Twelve monoclonal antibodies (MAbs) was generated using purified VP7 or CLPs as a source of antigen and were utilized for epitope mapping with available chimeric VP7 molecules and the RGD mutants. Several MAbs bound to the RGD motif on the core, as shown by immunogold labeling and cryoelectron microscopy. RGD-specific MAb H1.5, but not those directed to other regions of the core, inhibited the binding activity of CLPs to the Culicoides cell surface. Together, these data indicate that the RGD motif present on BTV VP7 is responsible for Culicoides cell binding activity.

Molecular modulation of calcium oxalate crystallization

2006 ◽  
Vol 291 (6) ◽  
pp. F1123-F1132 ◽  
Author(s):  
James J. De Yoreo ◽  
S. Roger Qiu ◽  
John R. Hoyer
Keyword(s):  
Molecular Modeling ◽  
Calcium Oxalate ◽  
Stone Formation ◽  
Energy Levels ◽  
Critical Role ◽  
Specific Interactions ◽  
Crystal Surfaces ◽  
Site Specific

Calcium oxalate monohydrate (COM) is the primary constituent of the majority of renal stones. Osteopontin (OPN), an aspartic acid-rich urinary protein, and citrate, a much smaller molecule, are potent inhibitors of COM crystallization at levels present in normal urine. Current concepts of the role of site-specific interactions in crystallization derived from studies of biomineralization are reviewed to provide a context for understanding modulation of COM growth at a molecular level. Results from in situ atomic force microscopy (AFM) analyses of the effects of citrate and OPN on growth verified the critical role of site-specific interactions between these growth modulators and individual steps on COM crystal surfaces. Molecular modeling investigations of interactions of citrate with steps and faces on COM crystal surfaces provided links between the stereochemistry of interaction and the binding energy levels that underlie mechanisms of growth modification and changes in overall crystal morphology. The combination of in situ AFM and molecular modeling provides new knowledge that will aid rationale design of therapeutic agents for inhibition of stone formation.

Head length determination in bacteriophage T4: The role of the core protein P22

1976 ◽  
Vol 103 (1) ◽  
pp. 155-174 ◽  
Author(s):  
James R. Paulson ◽  
Sara Lazaroff ◽  
Ulrich K. Laemmli
Keyword(s):  
Core Protein ◽  
Bacteriophage T4 ◽  
Head Length ◽  
The Core ◽  
Length Determination

scholarly journals Stepwise RNP assembly at the site of H/ACA RNA transcription in human cells

2006 ◽  
Vol 173 (2) ◽  
pp. 207-218 ◽  
Author(s):  
Xavier Darzacq ◽  
Nupur Kittur ◽  
Sujayita Roy ◽  
Yaron Shav-Tal ◽  
Robert H. Singer ◽  
...  
Keyword(s):  
Rna Splicing ◽  
Ribosome Biogenesis ◽  
Core Protein ◽  
Single Cells ◽  
Telomere Maintenance ◽  
Rna Transcription ◽  
The Core ◽  
Core Proteins ◽  
Rna Accumulation

Mammalian H/ACA RNPs are essential for ribosome biogenesis, premessenger RNA splicing, and telomere maintenance. These RNPs consist of four core proteins and one RNA, but it is not known how they assemble. By interrogating the site of H/ACA RNA transcription, we dissected their biogenesis in single cells and delineated the role of the non-core protein NAF1 in the process. NAF1 and all of the core proteins except GAR1 are recruited to the site of transcription. NAF1 binds one of the core proteins, NAP57, and shuttles between nucleus and cytoplasm. Both proteins are essential for stable H/ACA RNA accumulation. NAF1 and GAR1 bind NAP57 competitively, suggesting a sequential interaction. Our analyses indicate that NAF1 binds NAP57 and escorts it to the nascent H/ACA RNA and that GAR1 then replaces NAF1 to yield mature H/ACA RNPs in Cajal bodies and nucleoli.

scholarly journals Small but Stylish: Pushing Innovation Ambidexterity in International Small and Medium Enterprises

2020 ◽  
Vol 6 (2) ◽  
pp. 54
Author(s):  
Faizah Mashahadi ◽  
Noor Hazlina Ahmad
Keyword(s):  
Conceptual Model ◽  
Entrepreneurial Orientation ◽  
Industrial Revolution ◽  
Small And Medium Enterprises ◽  
Critical Role ◽  
Innovation Activity ◽  
The Core ◽  
Enhance Efficiency ◽  
Medium Enterprises

Small and Medium Enterprises (SMEs) have been the core agents in accelerating growth and providing jobs opportunities for the nation. Indeed, with industrial revolution rapidly evolving, there is a stronger exigency for SMEs to explore new opportunities aims to enhance efficiency so that SMEs able to compete and grow internationally. Recent development has heightened the need for SMEs to involve in innovation activity as the means to improve competitiveness and sustaining performance becoming a reality. Many studies emphasize on the critical role of innovation ambidexterity in determining SMEs success but the existing studies yet to conclude the predecessor of innovation ambidexterity in internationally operated SMEs. This article aims to provide a conceptual model that explores the potential of international entrepreneurial orientation in determining innovation ambidexterity in international SMEs in Malaysia.

scholarly journals Mutation in ATG5 reduces autophagy and leads to ataxia with developmental delay

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Myungjin Kim ◽  
Erin Sandford ◽  
Damian Gatica ◽  
Yu Qiu ◽  
Xu Liu ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Neurodegenerative Disorders ◽  
Neurological Diseases ◽  
Critical Role ◽  
Wild Type ◽  
Autophagy Flux ◽  
The Core ◽  
Atg Genes ◽  
Autophagy Pathway

Autophagy is required for the homeostasis of cellular material and is proposed to be involved in many aspects of health. Defects in the autophagy pathway have been observed in neurodegenerative disorders; however, no genetically-inherited pathogenic mutations in any of the core autophagy-related (ATG) genes have been reported in human patients to date. We identified a homozygous missense mutation, changing a conserved amino acid, in ATG5 in two siblings with congenital ataxia, mental retardation, and developmental delay. The subjects' cells display a decrease in autophagy flux and defects in conjugation of ATG12 to ATG5. The homologous mutation in yeast demonstrates a 30-50% reduction of induced autophagy. Flies in which Atg5 is substituted with the mutant human ATG5 exhibit severe movement disorder, in contrast to flies expressing the wild-type human protein. Our results demonstrate the critical role of autophagy in preventing neurological diseases and maintaining neuronal health.

Proteasome activator Blm10 regulates transcription especially during aging

2021 ◽  
Vol 22 ◽  
Author(s):  
Yu-Shan Chen ◽  
Xia Han ◽  
Kui Lin ◽  
Tian-Xia Jiang ◽  
Xiao-Bo Qiu
Keyword(s):  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Cellular Aging ◽  
Yeast Cells ◽  
Histone Marks ◽  
Proteasome Activator ◽  
The Core ◽  
Core Histones ◽  
The Stability

Background: Histones are basic elements of the chromatin, and are critical to controlling chromatin structure and transcription. The proteasome activator PA200 promotes the acetylation-dependent proteasomal degradation of the core histones during spermatogenesis, DNA repair, transcription and cellular aging, and maintains the stability of histone marks. Objective: The study aimed to explore whether the yeast ortholog of PA200, Blm10, promotes degradation of the core histones during transcription and regulates transcription especially during aging. Method: Protein degradation assays were performed to detect the role of Blm10 in histone degradation during transcription. mRNA profiles were compared in WT and mutant BY4741 or MDY510 yeast cells by RNA-sequencing. Results: The core histones can be degraded by the Blm10-proteasome in the non-replicating yeast, suggesting that Blm10 promotes the transcription-coupled degradation of the core histones. Blm10 preferentially regulates transcription in aged yeast, especially transcription of genes related to translation, amino acid metabolism and carbohydrate metabolism. Mutations of Blm10 at F2125/N2126 in its putative acetyl-lysine binding region abolished the Blm10-mediated regulation of gene expression. Conclusion: Blm10 promotes degradation of the core histones during transcription and regulates transcription especially during cellular aging, further supporting the critical role of PA200 in maintaining the stability of histone marks from the evolutionary view. These results should provide meaningful insights into the mechanisms underlying aging and the related diseases.

New insights into the mechanisms of lipid-body biogenesis in plants and other organisms

2000 ◽  
Vol 28 (6) ◽  
pp. 710-711 ◽  
Author(s):  
D.J. Murphy ◽  
I. Hernendez-Pinzon ◽  
K. Patel ◽  
R. G. Hope ◽  
J. McLauchlan
Keyword(s):  
Endoplasmic Reticulum ◽  
Calcium Binding ◽  
Core Protein ◽  
Animal Cell ◽  
Lipid Body ◽  
Comparative Approach ◽  
The Core ◽  
Wide Range ◽  
Powerful Approach

A comparative approach has been used to study the role of several lipid-body-binding proteins in plants and animals. Caleosins are a newly discovered class of calcium-binding lipid-body proteins found in plants and fungi, which we now report to have separate endoplasmic reticulum and lipid-body-associated isoforms. We also compare the lipid-body targeting of oleosin from plants and the core protein of the hepatitis C virus when they were expressed separately in lipid-accumulating animal cell lines. This is a novel and powerful approach to investigating the factors that determine the lipid-body targeting of a wide range of proteins.

scholarly journals A Critical Role of Non-active Site Residues on Cyclooxygenase Helices 5 and 6 in the Control of Prostaglandin Stereochemistry at Carbon 15

2007 ◽  
Vol 282 (38) ◽  
pp. 28157-28163 ◽  
Author(s):  
Karin Valmsen ◽  
William E. Boeglin ◽  
Reet Järving ◽  
Ivar Järving ◽  
Külliki Varvas ◽  
...  
Keyword(s):  
Amino Acid ◽  
Active Site ◽  
Amino Acid Sequence Identity ◽  
Critical Role ◽  
Site Directed Mutagenesis ◽  
Single Amino Acid ◽  
Active Site Residues ◽  
The Core ◽  
The Difference

The correct stereochemistry of prostaglandins is a prerequisite of their biological activity and thus is under a strict enzymatic control. Recently, we cloned and characterized two cyclooxygenase (COX) isoforms in the coral Plexaura homomalla that share 97% amino acid sequence identity, yet form prostaglandins with opposite stereochemistry at carbon 15. The difference in oxygenation specificity is only partially accounted for by the single amino acid substitution in the active site (Ile or Val at position 349). For further elucidation of residues involved in the C-15 stereocontrol, a series of sequence swapping and site-directed mutagenesis experiments between 15R- and 15S-COX were performed. Our results show that the change in stereochemistry at carbon 15 of prostaglandins relates mainly to five amino acid substitutions on helices 5 and 6 of the coral COX. In COX proteins, these helices form a helix-turn-helix motif that traverses through the entire protein, contributing to the second shell of residues around the oxygenase active site; it constitutes the most highly conserved region where even slight changes result in loss of catalytic activity. The finding that this region is among the least conserved between the P. homomalla 15S- and 15R-specific COX further supports its significance in maintaining the desired prostaglandin stereochemistry at C-15. The results are particularly remarkable because, based on its strong conservation, the conserved middle of helix 5 is considered as central to the core structure of peroxidases, of which COX proteins are derivatives. Now we show that the same parts of the protein are involved in the control of oxygenation with 15R or 15S stereospecificity in the dioxygenase active site.

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