Potyviral Genome-Linked Protein and its Interaction with Plant Defense Ribosome Inactivating Protein from Phytolacca Americana

Agriculture is an indispensable part of every person’s life, ensuring that nutritious and inexpensive food is readily available. Agriculture continues to be confronted with epidemics, having devastating effects on economies and the plant sources essential for human and animal life. Plants and their pathogens have developed evolutionary adaptations, each shaping the other’s defence and invasive strategies. Many different plants produce toxic ribosome inactivating proteins that aid in their defence mechanisms against pathogenic invaders. Viruses must adapt to the host translational machinery, several having evolved to include viral genome-linked proteins that carry numerous viral functions. Here, we review how a potyviral protein from turnip mosaic virus linked to its genome is able to inhibit pokeweed plant defence protein, and perhaps potentially conferring viral resistance to the toxin

Ethics Pertaining to the Legalities of Male Routine Infant Circumcision and Surrogate Consent to Non-Therapeutic Surgery

Circumcision is the most contentious surgery performed in the world today. Approximately 38% of the world male population has been circumcised, mostly during the neonatal and prepubescent periods. Circumcision in regularly practiced ubiquitously throughout the Islamic countries, Israel, and the United States; the US is only country who regularly circumcises its boys for a non-religious reason. No world health body advocates circumcision prior to adulthood. Routine Infant Circumcision (RIC) violates the United Nations Policy on Genital Integrity, the Hippocratic Oath taken by doctors, and the rules for surrogate consent to surgery. Studies have shown no benefits to circumcision during the neonatal period, and only potentially marginal benefits later in life. The decision of the parent to have their infant boy circumcised is a clear violation of the boys’ right to grow up naturally. Cultural and religious biases serve to make the subject of circumcision taboo, where an attack upon it is seen to be an assault on American culture or freedom of religion. Ethically the choice is clear, maintain the child of sound mind and body until he reaches the age of majority, at which point he may decide for himself whether or not to be circumcised. To do otherwise is to irrevocably alter the boys’ body and mind, destroying the most basic right, the right to bodily integrity

Inhibition of Pokeweed Antiviral Protein (PAP) by turnip mosaic virus genome-linked protein (VPg)

Pokeweed antiviral protein (PAP) from Phytolacca americana is a ribosome-inactivating protein (RIP) and an RNA N-glycosidase that removes specific purine residues from the sarcin/ricin loop of large rRNA, arresting protein synthesis at the translocation step. PAP is also a cap-binding protein and is a potent antiviral agent against many plant, animal, and human viruses. To elucidate the mechanism of RNA depurination, and to understand how PAP recognizes and targets various RNAs, the interactions between PAP and turnip mosaic virus genomelinked protein (VPg) were investigated. VPg can function as a cap analog in cap-independent translation and potentially target PAP to uncapped IRES-containing RNA. In this work, fluorescence spectroscopy andHPLCtechniques were used to quantitatively describe PAP depurination activity and PAP-VPg interactions. PAP binds to VPg with high affinity (29.5 nM); the reaction is enthalpically driven and entropically favored. Further, VPg is a potent inhibitor of PAP depurination of RNA in wheat germ lysate and competes with structured RNA derived from tobacco etch virus for PAP binding. VPg may confer an evolutionary advantage by suppressing one of the plant defense mechanisms and also suggests the possible use of this protein against the cytotoxic activity of ribosome-inactivating proteins. Background: PAP is a ribosome-inactivating protein that depurinates RNA and inhibits protein synthesis. Results: Turnip mosaic VPg inhibits enzymatic activity of PAP in wheat germ extract. Conclusion: VPg may play a role in overcoming viral resistance by suppressing the plant defense mechanism. Significance: Depurination inhibition by VPg suggests a novel viral strategy to evade host cell defense and possible anticytotoxic activity against RIPs

Insights into the Molecular Antiviral Mechanism of Pokeweed Protein from Phytolacca americana

Agriculture is an indispensable part of every person’s life, ensuring that nutritious and inexpensive food is readily available. As any other organisms, plants are subject to numerous parasitic infections. Biological evolution has allowed plants to produce a variety of toxic compounds to deal with their pathogens. American pokeweed plant (Phytolacca americana) manufactures pokeweed antiviral protein, a ribosome inactivating protein that disrupts protein synthesis and lowers infectivity of many plant and animal viruses. The intricate mechanism of PAP antiviral activity entails a delicate coordination and interplay of several factors, allowing the plant to battle its invaders. Here, we examine the molecular mechanism of this plant peptide, and describe a molecular model of pokeweed’s antiviral activity

Pokeweed Antiviral Protein, a Ribosome Inactivating Protein: Activity, Inhibition and Prospects

Viruses employ an array of elaborate strategies to overcome plant defense mechanisms and must adapt to the requirements of the host translational systems. Pokeweed antiviral protein (PAP) from Phytolacca americana is a ribosome inactivating protein (RIP) and is an RNA N-glycosidase that removes specific purine residues from the sarcin/ricin (S/R) loop of large rRNA, arresting protein synthesis at the translocation step. PAP is thought to play an important role in the plant’s defense mechanism against foreign pathogens. This review focuses on the structure, function, and the relationship of PAP to other RIPs, discusses molecular aspects of PAP antiviral activity, the novel inhibition of this plant toxin by a virus counteraction—a peptide linked to the viral genome (VPg), and possible applications of RIP-conjugated immunotoxins in cancer therapeutics

Iron response elements (IREs)-mRNA of Alzheimer's amyloid precursor protein binding to iron regulatory protein (IRP1): a combined molecular docking and spectroscopic approach

Abstract The interaction between the stem-loop structure of the Alzheimer's amyloid precursor protein IRE mRNA and iron regulatory protein was examined by employing molecular docking and multi-spectroscopic techniques. A detailed molecular docking analysis of APP IRE mRNA∙IRP1 reveals that 11 residues are involved in hydrogen bonding as the main driving force for the interaction. Fluorescence binding results revealed a strong interaction between APP IRE mRNA and IRP1 with a binding affinity and an average binding sites of 31.3 × 106 M−1 and 1.0, respectively. Addition of Fe2+(anaerobic) showed a decreased (3.3-fold) binding affinity of APP mRNA∙IRP1. Further, thermodynamic parameters of APP mRNA∙IRP1 interactions were an enthalpy-driven and entropy-favored event, with a large negative ΔH (–25.7 ± 2.5 kJ/mol) and a positive ΔS (65.0 ± 3.7 J/mol·K). A negative ΔH value for the complex formation suggested the contribution of hydrogen bonds and van der Waals forces. The addition of iron increased the enthalpic contribution by 38% and decreased the entropic influence by 97%. Furthermore, the stopped-flow kinetics of APP IRE mRNA∙IRP1 also confirmed the complex formation, having the rate of association (k on) and the rate of dissociation (k off) as 341 μM−1 s−1, and 11 s−1, respectively. The addition of Fe2+ has decreased the rate of association (k on) by ~ three-fold, whereas the rate of dissociation (k off) has increased by ~ two-fold. The activation energy for APP mRNA∙IRP1 complex was 52.5 ± 2.1 kJ/mol. The addition of Fe2+ changed appreciably the activation energy for the binding of APP mRNA with IRP1. Moreover, circular dichroism spectroscopy has confirmed further the APP mRNA∙IRP1 complex formation and IRP1 secondary structure change with the addition of APP mRNA. In the interaction between APP mRNA and IRP1, iron promotes structural changes in the APP IRE mRNA∙IRP1 complexes by changing the number of hydrogen bonds and promoting a conformational change in the IRP1 structure when it is bound to the APP IRE mRNA. It further illustrates how IRE stem-loop structure influences selectively the thermodynamics and kinetics of these protein-RNA interactions