Quantum theory is traditionally formulated using complex numbers. This imaginarity of quantum has been quantified as a resource with applications in discrimination tasks, pseudorandomness generation, and metrology. In the standard formulation, state said to have "imaginarity" if associated density matrix not real-valued given, fixed basis. If instead we consider set states, it possible devise tests that guarantee some set, independently basis chosen. Here propose such basis-independent...

We present the first structure of human Kir2.1 channel containing both transmembrane domain (TMD) and cytoplasmic (CTD). channels are strongly inward-rectifying potassium that play a key role in maintaining resting membrane potential. Their gating is modulated by phosphatidylinositol 4,5-bisphosphate (PIP 2 ). Genetically inherited defects responsible for several rare diseases, including Andersen’s syndrome. The structural analysis (cryo–electron microscopy), surface plasmon resonance,...

Phospholipases A(2) (Asp49-PLA(2)s) are enzymes responsible for cellular membrane disruption through Ca(2+)-dependent hydrolysis of phospholipids. A class these proteins (Lys49-PLA(2)s) does not show catalytic activity but can exert a pronounced local myotoxic effect that is neutralized by serum therapy. In this work, we present five structures Lys49-PLA(2)s from snakes the Bothrops genus in apo form, complexed with PEG molecules and chemically modified p-bromofenacil bromide (BPB), classic...

Abstract Phospholipases A 2 (PLA s) are enzymes responsible for membrane disruption through Ca 2+ ‐dependent hydrolysis of phospholipids. Lys49‐PLA s well‐characterized homologue PLA that do not show catalytic activity but can exert a pronounced local myotoxic effect. These were first believed to present residual experiments with recombinant toxin they incapable catalysis. Herein, we new Asp49‐PLA (BthTX‐II) is also able muscle damage. This was isolated in 1992 and characterized as...

One of the main challenges in toxicology today is to develop therapeutic alternatives for treatment snake venom injuries that are not efficiently neutralized by conventional serum therapy. Venom phospholipases A2 (PLA2s) and PLA2-like proteins play a fundamental role skeletal muscle necrosis, which can result permanent sequelae disability. This leads economic social problems, especially developing countries. In this work, we performed structural functional studies with Piratoxin-I,...

Bothrops brazili is a snake found in the forests of Amazonian region whose commercial therapeutic anti-bothropic serum has low efficacy for local myotoxic effects, resulting an important public health problem this area. Catalytically inactive phospholipases A2-like (Lys49-PLA2s) are among main components from genus venoms and capable causing drastic myonecrosis. Several studies have shown that C-terminal these toxins, which includes variable combination positively charged hydrophobic...

Replication Protein A (RPA), the major single stranded DNA binding protein in eukaryotes, is composed of three subunits and a fundamental player metabolism, participating replication, transcription, repair, damage response. In human pathogenic trypanosomatids, only limited studies have been performed on RPA-1 from Leishmania. Here, we silico, vitro vivo analysis Trypanosoma cruzi RPA-2 subunits. Although computational suggests similarities Ob-fold structures RPA T. compared with mammalian...

One of the main challenges in snakebite envenomation treatment is development stable, versatile and efficient anti-venom therapies. Local myotoxicity accidents involving snakes from Bothrops genus still a consequence serum therapy inefficient neutralization that may lead to permanent sequelae their victims. classes toxins participate muscle necrosis PLA2-like proteins. The aim this work was investigate role zinc ions inhibition proteins advance current knowledge action mechanism.Myographic...

For the first time, structure of a catalytic inactive phospholipase A2 homolog (Lys49-PLA2s) complexed with p-bromophenacyl bromide (BPB) has been solved by X-ray crystallography. Lys49-PLA2s are among main components Viperidae snake venoms, causing myonecrosis and other actions despite their inactivity. BPB, classic inhibitor catalytic-active PLA2s, used since 1970s because it binds specifically His48 residue site. Curiously, when Lys49-PLA2 is chemically modified causes partial inhibition...

Abstract Crotoxin (CTX) is the main neurotoxin found in Crotalus durissus rattlesnake venoms being composed by a nontoxic and non-enzymatic component (CA) toxic phospholipase A 2 (CB). Previous crystallographic structures of CTX CB provided relevant insights: (i) structure showed 1:1 molecular ratio between CA CB, presenting three tryptophan residues CA/CB interface one exposed to solvent; (ii) displayed tetrameric conformation. This study aims provide further information on mechanism action...

Abstract Inwardly rectifying potassium (Kir) channels play a pivotal role in physiology by establishing, maintaining, and regulating the resting membrane potential of cells, particularly contributing to cellular repolarization many excitable cells. Dysfunction Kir2.1 is implicated several chronic debilitating human diseases for which there are currently no effective treatments. Specifically, Kir2.1-R312H Kir2.1-C154Y mutations associated with Andersen-Tawil syndrome (ATS) humans. We have...

Phospholipases A(2) (PLA(2)s) are important components of Bothrops snake venoms, that can induce several effects on envenomations such as myotoxicity, inhibition or induction platelet aggregation and edema. It is known venomous non-venomous snakes present PLA(2) inhibitory proteins (PLIs) in their blood plasma. An protein neutralizes the enzymatic toxic activities PLA(2)s from venoms was isolated alternatus plasma by affinity chromatography using immobilized myotoxin BthTX-I CNBr-activated...

Crotoxin is a neurotoxin from Crotalus durissus terrificus venom that shows immunomodulatory, anti-inflammatory, antimicrobial, antitumor and analgesic activities. Structurally, this toxin heterodimeric complex composed by toxic basic PLA2 (Crotoxin B or CB) non-covalently linked to an atoxic non-enzymatic acidic component (Crotapotin, A CA). Several CA CB isoforms have been isolated characterized, showing the crotoxin fraction is, in fact, mixture of different molecules derived combination...

The mortality caused by snakebites is more damaging than many tropical diseases, such as dengue haemorrhagic fever, cholera, leishmaniasis, schistosomiasis and Chagas disease. For this reason, snakebite envenoming adversely affects health services of subtropical countries recognized a neglected disease the World Health Organization. One main components snake venoms Lys49-phospholipases A2, which catalytically inactive but possesses other toxic pharmacological activities. Preliminary studies...

Replication protein A‐1 (RPA‐1) is a single‐stranded DNA‐binding involved in DNA metabolism. We previously demonstrated the interaction between LaRPA‐1 and telomeric DNA. Here, we expressed purified truncated mutants of used circular dichroism measurements molecular dynamics simulations to demonstrate that tertiary structure differs from human yeast RPA‐1. interacts with ssDNA via its N‐terminal OB‐fold domain, whereas RPA higher eukaryotes show different binding modes ssDNA. Our results...

One of the main components snake venoms are Asp49-phospholipases A(2), also known as svPLA(2)s. The study these toxins is a matter great scientific interest due to their wide variety biological effects. In this work we present strong evidences found in literature and other aspects which strengthen importance quaternary assembly for understanding activities molecular evolution

Phospholipases A2 are major components of snake venoms (svPLA2s) and able to induce multiple local systemic deleterious effects upon envenomation. Several species provided with svPLA2 inhibitors (sbPLIs) in their circulating blood, which confer a natural resistance against the toxic homologous heterologous venoms. The sbPLIs belong any three structural classes named α, β γ. In present study, we identified, characterized performed evolutionary analyses sbαPLIs transcripts encoded proteins,...

Background: We evaluated the impacts of corona protein (CP) formation on alternating current biosusceptometry (ACB) signal intensity and in vivo circulation times three differently coated magnetic nanoparticles (MNP): bare, citrate-coated bovine serum albumin-coated MNPs. Methods: employed ACB system, gel electrophoresis mass spectrometry analysis. Results: Higher CP led to a greater reduction vitro time. found fewer proteins forming for MNPs, which presented highest time among MNPs studied....

Abstract Inwardly rectifying potassium (Kir) channels play a pivotal role in physiology by establishing, maintaining, and regulating the resting membrane potential of cells, particularly contributing to cellular repolarization many excitable cells. Dysfunction Kir2.1 is implicated several chronic debilitating human diseases for which there are currently no effective treatments. Specifically, Kir2.1‐R312H Kir2.1‐C154Y mutations associated with Andersen‐Tawil syndrome (ATS) humans. We have...