Publications by authors named "Laercio Pol-Fachin"

Background: Sleep deficits caused by the overuse of digital technology is observed among medical students. Due to the coronavirus disease 2019 (COVID-19) pandemic, an emergency remote teaching method was put into practice, which may have resulted in changes in the sleep-wake cycle. The balance between the influences of external and internal synchronizers can be affected by sudden alterations in daily life, including changes in nightly habits and sleep quality, which can lead to increased levels of anxiety and reduced functional performance, for example.

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Root hairs (RHs) develop from specialized epidermal trichoblast cells, whereas epidermal cells that lack RHs are known as atrichoblasts. The mechanism controlling RH cell fate is only partially understood. RH cell fate is regulated by a transcription factor complex that promotes the expression of the homeodomain protein GLABRA 2 (GL2), which blocks RH development by inhibiting ROOT HAIR DEFECTIVE 6 (RHD6).

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Lipid-linked oligosaccharides (LLOs) play an important role in the N-glycosylation pathway as the donor substrate of oligosaccharyltransferases (OSTs), which are responsible for the transfer of glycan chains onto a nascent polypeptide. The lipid component of LLO in both eukarya and archaea consists of a dolichol, and an undecaprenol in prokarya, whereas the number of isoprene units may change between species. Given the potential relevance of LLOs and their related enzymes to diverse biotechnological applications, obtaining reliable LLO models from distinct domains of life could support further studies on complex formation and their processing by OSTs, as well as protein engineering on such systems.

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Microcystins (MCs) are a class of cyclic heptapeptides with more than 100 variants produced by cyanobacteria present in surface waters. MCs are potent hepatotoxic agents responsible for fatal poisoning in animals and humans. Several techniques are employed in the detection of MCs, however, there is a shortage of methods capable of discriminating variants of MCs.

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The ability of erythrocytes, infected by Plasmodium falciparum, to adhere to endothelial cells (cytoadherence) and to capture uninfected erythrocyte (rosetting) is the leading cause of death by severe malaria. Evidences link the binding of the adhesin Duffy Binding Like1-α (DBL1α) domain to the ABH histo-blood antigens with formation of rosettes. Inspired by this very close relationship between the disease susceptibility and individual blood type, here we investigate the structural requirements involved in the interaction of DBL1α with A, B and H histo-blood determinants and their subtypes.

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Article Synopsis
  • * Despite a 55% average sequence identity between ZIKV NS1 and dengue virus (DENV) serotypes, the identified epitope sequences are highly conserved, though flanking residues differ significantly.
  • * These differences in flanking residues lead to varied electrostatic properties, suggesting that using short linear NS1 sequences for distinguishing Zika from dengue may be ineffective due to potential cross-reactions.
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Lipid-A is the causative agent of Gram-negative sepsis and is responsible for an increasingly high mortality rate among hospitalized patients. Compounds that bind Lipid-A can limit this inflammatory process. The cationic antimicrobial peptide polymyxin B (Pmx-B) is one of the simplest molecules capable of selectively binding to Lipid-A and may serve as a model for further development of Lipid-A binding agents.

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δ-Toxin is a 26 amino acid peptide capable of lysing several mammalian cell types and subcellular structures. Structurally, δ-toxin predominantly exhibits a α-helical secondary structure in membranes but, in aqueous solution, it adopts varying helical content. As no atomic-level data is available for this peptide in aqueous solutions and for the water-to-membrane transition, this work aims to characterize δ-toxin behavior in these conditions through molecular dynamics simulations in triplicates employing four different parameter sets.

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CrataBL is a glycoprotein isolated from Crataeva tapia bark, containing two N-glycosylation sites. It has been identified to present lectin activity with some specificity for binding glucose over galactose. However, to date, no information on the effects of glycosylation or CrataBL monosaccharide-binding sites and monosaccharide specificity has been obtained.

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The epidermal growth factor receptor (EGFR) is an important transmembrane glycoprotein kinase involved the initiation or perpetuation of signal transduction cascades within cells. These processes occur after EGFR binds to a ligand [epidermal growth factor (EGF)], thus inducing its dimerization and tyrosine autophosphorylation. Previous publications have highlighted the importance of glycosylation and dimerization for promoting proper function of the receptor and conformation in membranes; however, the effects of these associations on the protein conformational stability have not yet been described.

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Gaucher disease, an autosomal recessive disorder, is caused by a deficiency of glucocerebrosidase (GCase) enzyme, a peripheral membrane-associated glycoprotein that hydrolyses glucosylceramide in lysosomes. Glycosylation is essential for the development of a catalytically active enzyme, specifically in the first site, located at Asn19. However, both the molecular basis of the relevance of N-glycosylation over GCase activity and the effects of glycosylation over its structure and dynamics are still not fully understood.

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A great number of pathogens secrete pore-forming proteins during infection. Such molecules, from either bacterial or viral origin, are considered important virulence factors, which makes them attractive targets in the study of new therapeutic agents. Thus, the inhibitory activity of isatin-Schiff base copper(II) complexes was evaluated against membrane damage activity of Staphylococcus aureus α-hemolysin (α-HL).

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The major cat allergen, Fel d 1, is a structurally complex protein with two N-glycosylation sites that may be filled by different glycoforms. In addition, the protein contains three putative Ca2+ binding sites. Since the impact of these Fel d 1 structure modifications on the protein dynamics, physiology and pathology are not well established, the present work employed computational biology techniques to tackle these issues.

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Mutants of the O-glycosylation pathway of extensins as well as molecular dynamics simulations uncover the effects of the O-glycosylation machinery on root hair tip growth.

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An extension of the GROMOS 53A6GLYC force field for carbohydrates to encompass glycoprotein linkages is presented. The set includes new atomic charges and incorporates adequate torsional potential parameters for N-, S-, C-, P-, and O-glycosydic linkages, offering compatibility with the GROMOS force field family for proteins. Validation included the description of glycosydic linkage geometries between amino acid and monosaccharide residues, comparison of NMR-derived protein-carbohydrate and carbohydrate-carbohydrate nuclear overhauser effect (NOE) signals for glycoproteins and the effects of glycosylation on protein flexibility and dynamics.

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QS-21 is a saponin extracted from Quillaja saponaria, widely investigated as a vaccine immunoadjuvant. However, QS-21 use is mainly limited by its chemical instability, significant variety in molecular composition and low tolerance dose in mammals. Also, this compound tends to form micelles in a concentration-dependent manner.

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The structurally diverse polysaccharide lyase enzymes are distributed from plants to animals but share common catalytic mechanisms. One, heparinase I (F. heparinum), is employed in the production of the major anticoagulant drug, low molecular weight heparin, and is a mainstay of cell surface proteoglycan analysis.

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fIIa and fXa are two of the main targets of antithrombin, a serine proteases inhibitor that plays a major role in the regulation of blood clotting. The formation of ternary complexes between such molecules and glycosaminoglycans, as heparin, is the main path for inhibiting those enzymes, which may occur through two distinct mechanisms of action. While these serine proteases present distinct susceptibilities to these paths, in which fIIa demands an interaction with heparin, neither the molecular basis of this differential inhibition nor the role of fIIa glycosylation on this process is fully understood.

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Sulfation patterns along glycosaminoglycan (GAG) chains dictate their functional role. The N-deacetylase N-sulfotransferase family (NDST) catalyzes the initial downstream modification of heparan sulfate and heparin chains by removing acetyl groups from subsets of N-acetylglucosamine units and, subsequently, sulfating the residual free amino groups. These enzymes transfer the sulfuryl group from 3'-phosphoadenosine-5'-phosphosulfate (PAPS), yielding sulfated sugar chains and 3'-phosphoadenosine-5'-phosphate (PAP).

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Arylsulfatase A (ARSA) is a lysosomal sulfatase that catalyzes the hydrolysis of cerebroside sulfate. Its deficiency results in Metachromatic Leukodystrophy, whereas a minor condition called ARSA pseudodeficiency occurs in healthy individuals, which has been associated with the substitution of the glycosylated Asn350 by a Ser and with the loss of the polyadenylation signal. In this work, we have investigated ARSA dynamics employing molecular dynamics simulations in response to (1) different pH's, as, beyond its natural lysossomal environment, it has been recently identified in cytoplasmatic medium and (2) glycan occupancies, including its normal glycosylation state, presenting three high mannose-type oligosaccharides.

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A highly sulfated 3-linked β-arabinan (Ab1) with arabinose in the pyranose form was obtained from green seaweed Codium vermilara (Bryopsidales). It comprised major amounts of units sulfated on C-2 and C-4 and constitutes the first polysaccharide of this type isolated in the pure form and fully characterized. Ab1 showed anticoagulant activity by global coagulation tests.

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An improved parameter set for explicit-solvent simulations of carbohydrates (referred to as GROMOS 53A6GLYC) is presented, allowing proper description of the most stable conformation of all 16 possible aldohexopyranose-based monosaccharides. This set includes refinement of torsional potential parameters associated with the determination of hexopyranose rings conformation by fitting to their corresponding quantum-mechanical profiles. Other parameters, as the rules for third and excluded neighbors, are taken directly from the GROMOS 53A6 force field.

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Saponins are secondary metabolites that have a plethora of biological activities. However, the absence of knowledge of their 3D structures is a major drawback for structural-based strategies in medicinal chemistry. To address this problem, the current work presents structural models of Stenocereus eruca saponins, named erucasaponin A and stellatoside B.

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Art v 1 is the major allergen of mugwort (Artemisia vulgaris) pollen. It is formed by an N-terminal globular defensin-like part and a C-terminal proline-rich domain. As the structure and the dynamics of Art v 1 have been mostly described for its recombinant, non-glycosylated form, which does not occur in normal plant physiology, the present work intends to obtain a three-dimensional model for Art v 1 native O-glycosylation structure and to evaluate the influence of such glycans over the protein dynamics and allergenicity through molecular dynamics simulations in triplicates.

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Antithrombin (AT), a serine protease inhibitor, circulates in blood in two major isoforms, α and β, which differ in their amount of glycosylation and affinity for heparin. After binding to this glycosaminoglycan, the native AT conformation, relatively inactive as a protease inhibitor, is converted to an activated form. In this process, β-AT presents the higher affinity for heparin, being suggested as the major AT glycoform inhibitor in vivo.

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