Structure and dynamics of Alpha B.1.1.7 SARS-CoV-2 S-protein in complex with Fab of neutralizing antibody REGN10987.

One of the approaches for treatment of COVID-19 is a use of neutralizing antibodies (nAbs). The study of the mechanisms by which nAbs recognize different strains of SARS-CoV-2 may facilitate the development of new drugs and vaccines against the coronavirus infection. In this work, we present the 3.

Sea Anemone Kunitz Peptide HCIQ2c1 Reduces Histamine-, Lipopolysaccharide-, and Carrageenan-Induced Inflammation via the Suppression of Pro-Inflammatory Mediators.

Inflammation is a physiological response of the immune system to infectious agents or tissue injury, which involves a cascade of vascular and cellular events and the activation of biochemical pathways depending on the type of harmful agent and the stimulus generated. The Kunitz peptide HCIQ2c1 of sea anemone is a strong protease inhibitor and exhibits neuroprotective and analgesic activities. In this study, we investigated the anti-inflammatory potential of HCIQ2c1 in histamine- and lipopolysaccharide (LPS)-activated RAW 264.

Toxins from Animal Venom-A Rich Source of Active Compounds with High Pharmacological Potential.

Animal venoms contain a huge variety of bioactive molecules-namely, toxins-with an almost combinatorial spectrum of biological activities [...

Sea Anemone Kunitz Peptide HCIQ2c1: Structure, Modulation of TRPA1 Channel, and Suppression of Nociceptive Reaction In Vivo.

TRPA1 is a homotetrameric non-selective calcium-permeable channel. It contributes to chemical and temperature sensitivity, acute pain sensation, and development of inflammation. HCIQ2c1 is a peptide from the sea anemone that inhibits serine proteases.

Structure and dynamics of the interaction of Delta and Omicron BA.1 SARS-CoV-2 variants with REGN10987 Fab reveal mechanism of antibody action.

Study of mechanisms by which antibodies recognize different viral strains is necessary for the development of new drugs and vaccines to treat COVID-19 and other infections. Here, we report 2.5 Å cryo-EM structure of the SARS-CoV-2 Delta trimeric S-protein in complex with Fab of the recombinant analog of REGN10987 neutralizing antibody.

In Search of the Role of Three-Finger Starfish Proteins.

Three-finger proteins (TFPs), or Ly6/uPAR proteins, are characterized by the beta-structural LU domain containing three protruding "fingers" and stabilized by four conserved disulfide bonds. TFPs were initially characterized as snake alpha-neurotoxins, but later many studies showed their regulatory roles in different organisms. Despite a known expression of TFPs in vertebrates, they are poorly studied in other taxa.

Dimerization of the β-Hairpin Membrane-Active Cationic Antimicrobial Peptide Capitellacin from Marine Polychaeta: An NMR Structural and Thermodynamic Study.

Capitellacin is the β-hairpin membrane-active cationic antimicrobial peptide from the marine polychaeta . Capitellacin exhibits antibacterial activity, including against drug-resistant strains. To gain insight into the mechanism of capitellacin action, we investigated the structure of the peptide in the membrane-mimicking environment of dodecylphosphocholine (DPC) micelles using high-resolution NMR spectroscopy.

Recombinant Production, NMR Solution Structure, and Membrane Interaction of the Phα1β Toxin, a TRPA1 Modulator from the Brazilian Armed Spider .

Phα1β (PnTx3-6) is a neurotoxin from the spider venom, originally identified as an antagonist of two ion channels involved in nociception: N-type voltage-gated calcium channel (Ca2.2) and TRPA1. In animal models, Phα1β administration reduces both acute and chronic pain.

Specific Binding of the α-Component of the Lantibiotic Lichenicidin to the Peptidoglycan Precursor Lipid II Predetermines Its Antimicrobial Activity.

To date, a number of lantibiotics have been shown to use lipid II-a highly conserved peptidoglycan precursor in the cytoplasmic membrane of bacteria-as their molecular target. The α-component (Lchα) of the two-component lantibiotic lichenicidin, previously isolated from the VK21 strain, seems to contain two putative lipid II binding sites in its -terminal and -terminal domains. Using NMR spectroscopy in DPC micelles, we obtained convincing evidence that the -terminal mersacidin-like site is involved in the interaction with lipid II.

Orientational Preferences of GPI-Anchored Ly6/uPAR Proteins.

Ly6/uPAR proteins regulate many essential functions in the nervous and immune systems and epithelium. Most of these proteins contain single β-structural LU domains with three protruding loops and are glycosylphosphatidylinositol (GPI)-anchored to a membrane. The GPI-anchor role is currently poorly studied.

Membrane-mediated interaction of non-conventional snake three-finger toxins with nicotinic acetylcholine receptors.

Nicotinic acetylcholine receptor of α7 type (α7-nAChR) presented in the nervous and immune systems and epithelium is a promising therapeutic target for cognitive disfunctions and cancer treatment. Weak toxin from Naja kaouthia venom (WTX) is a non-conventional three-finger neurotoxin, targeting α7-nAChR with weak affinity. There are no data on interaction mode of non-conventional neurotoxins with nAChRs.

New Three-Finger Protein from Starfish Shares Structure and Pharmacology with Human Brain Neuromodulator Lynx2.

Three-finger proteins (TFPs) are small proteins with characteristic three-finger β-structural fold stabilized by the system of conserved disulfide bonds. These proteins have been found in organisms from different taxonomic groups and perform various important regulatory functions or act as components of snake venoms. Recently, four TFPs (Lystars 1-4) with unknown function were identified in the coelomic fluid proteome of starfish .

N Chemical Shifts and -Couplings as Diagnostic Tools for Determination of the Azide-Tetrazole Equilibrium in Tetrazoloazines.

Selectively N-labeled tetrazolo[1,5-][1,2,4]triazines and tetrazolo[1,5-]pyrimidines bearing one, two, or three N labels were synthesized. The synthesized compounds were studied by H, C, and N NMR spectroscopy in DMSO and TFA solutions, where the azide-tetrazole equilibrium can lead to the formation of two tetrazole (, ) isomers and one azide () isomer for each compound. Incorporation of the N-label(s) leads to the appearance of N-N coupling constants (), which can be easily measured via simple 1D N NMR spectra, even at natural abundance between labeled and unlabeled N atoms.

Probing GFP Chromophore Analogs as Anti-HIV Agents Targeting LTR-III G-Quadruplex.

Green fluorescent protein (GFP) chromophore and its congeners draw significant attention mostly for bioimaging purposes. In this work we probed these compounds as antiviral agents. We have chosen LTR-III DNA G4, the major G-quadruplex (G4) present in the long terminal repeat (LTR) promoter region of the human immunodeficiency virus-1 (HIV-1), as the target for primary screening and designing antiviral drug candidates.

SLURP-1 Controls Growth and Migration of Lung Adenocarcinoma Cells, Forming a Complex With α7-nAChR and PDGFR/EGFR Heterodimer.

Secreted Ly6/uPAR-related protein 1 (SLURP-1) is a secreted Ly6/uPAR protein that negatively modulates the nicotinic acetylcholine receptor of α7 type (α7-nAChR), participating in control of cancer cell growth. Previously we showed, that a recombinant analogue of human SLURP-1 (rSLURP-1) diminishes the lung adenocarcinoma A549 cell proliferation and abolishes the nicotine-induced growth stimulation. Here, using multiplex immunoassay, we demonstrated a decrease in PTEN and mammalian target of rapamycin (mTOR) kinase phosphorylation in A549 cells upon the rSLURP-1 treatment pointing on down-regulation of the PI3K/AKT/mTOR signaling pathway.

Dodecapeptide Cathelicidins of Cetartiodactyla: Structure, Mechanism of Antimicrobial Action, and Synergistic Interaction With Other Cathelicidins.

In this study, dodecapeptide cathelicidins were shown to be widespread antimicrobial peptides among the clade. In particular, we investigated the dodecapeptide from the domestic goat , designated as ChDode and its unique ortholog from the sperm whale (PcDode). ChDode contains two cysteine residues, while PcDode consists of two dodecapeptide building blocks and contains four cysteine residues.

Gausemycins A,B: Cyclic Lipoglycopeptides from Streptomyces sp.*.

We report a novel family of natural lipoglycopeptides produced by Streptomyces sp. INA-Ac-5812. Two major components of the mixture, named gausemycins A and B, were isolated, and their structures were elucidated.

Antiviral drug Triazavirin, selectively labeled with H, C, and N stable isotopes. Synthesis and properties.

Unlabelled: Isotope-labeled antiviral drug Triazavirin containing H, C, and N atoms in its structure has been synthesized. CHI and KSCN served as donors of C isotopes. The use of С-MeI containing H atoms made it possible to additionally incorporate deuterium labels into the structure of the compound.

Structure Elucidation and Functional Studies of a Novel β-hairpin Antimicrobial Peptide from the Marine Polychaeta .

Endogenous antimicrobial peptides (AMPs) are evolutionary ancient molecular factors of innate immunity that play a key role in host defense. Among the most active and stable under physiological conditions AMPs are the peptides of animal origin that adopt a β-hairpin conformation stabilized by disulfide bridges. In this study, a novel BRICHOS-domain related AMP from the marine polychaeta , named capitellacin, was produced as the recombinant analogue and investigated.

Mambalgin-2 Induces Cell Cycle Arrest and Apoptosis in Glioma Cells via Interaction with ASIC1a.

Gliomas are fast growing and highly invasive brain tumors, characterized by tumor microenvironment acidification that drives glioma cell growth and migration. Channels containing Acid-sensing Ion Channel 1a subunit (ASIC1a) mediate amiloride-sensitive cation influx in late stage glioma cells, but not in normal astrocytes. Thus, selective targeting of ASIC1a can be a perspective strategy for glioma treatment.

Water-soluble variant of human Lynx1 positively modulates synaptic plasticity and ameliorates cognitive impairment associated with α7-nAChR dysfunction.

Lynx1 is a GPI-tethered protein colocalized with nicotinic acetylcholine receptors (nAChRs) in the brain areas important for learning and memory. Previously, we demonstrated that at low micromolar concentrations the water-soluble Lynx1 variant lacking GPI-anchor (ws-Lynx1) acts on α7-nAChRs as a positive allosteric modulator. We hypothesized that ws-Lynx1 could be used for improvement of cognitive processes dependent on nAChRs.