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Spider venoms are complex mixtures of neurotoxic peptides, proteins and low molecular mass organic molecules. Their neurotoxic activity is due to the interaction of the venom components with cellular receptors, in particular ion channels. Spider venoms have proven to be a rich source of highly specific peptide ligands for selected subtypes of potassium, sodium and calcium channels, and these toxins...
Caenorhabditis elegans has become one of the most widely used model organisms for a range of molecular cell biological applications and is being increasingly used by glycobiologists. However, a major problem has been the lack of knowledge of the structure of the protein-linked glycans from this organism. In recent years several groups have published structural data, particularly N-glycan structural...
Three Plasmodium falciparum serine repeat antigen (SERA) protein peptides were studied by NMR and structure calculations being done in 70:30 water:trifluoroethanol solution. Peptide 22834 was shown to be immunogenic and protective against malaria in Aotus monkeys, whilst native peptide 6737 and its analogue 14096 did not present protection against the disease in these monkeys. Results showed a relationship...
Matrix Metalloproteinases (MMPs) are a family of multidomain zinc endopeptidases that function in the extracellular space or attached to the cell membrane. Their proteolytic activity is controlled by the presence of endogenous inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), α-macroglobulin and others. Disruption of the proteinase-inhibitor balance is observed in serious diseases...
Recent advances in X-ray crystallography have greatly contributed to the understanding of the structural interactions between aminoglycosides and the ribosomal decoding site. Efforts to genetically probe the functional relevance of proposed drug–nucleotide contacts have in part been hampered by the presence of multiple rRNA operons in most bacteria. A derivative of the Gram-positive Mycobacterium...
Dimerization of the genomic RNA is an important step of the HIV-1 replication cycle. The Dimerization Initiation Site (DIS) promotes dimerization of the viral genome by forming a loop–loop complex between two DIS hairpins. Crystal structures of the DIS loop–loop complex revealed an unexpected and strong similitude with the bacterial 16S ribosomal aminoacyl-tRNA site (A site), which is the target of...
Snake venom metalloproteinases (SVMPs) are multifunctional enzymes involved in several symptoms following snakebite, such as severe local hemorrhage. Multidomain P-III SVMPs are strongly hemorrhagic, whereas single domain P-I SVMPs are not. This indicates that disintegrin-like and cysteine-rich domains allocate motifs that enable catalytic degradation of ECM components leading to disruption of capillary...
Living cells contain a variety of biomolecules including nucleic acids, proteins, polysaccharides, and metabolites as well as other soluble and insoluble components. These biomolecules occupy a significant fraction (20–40%) of the cellular volume. The total concentration of biomolecules reaches 400gL −1 , leading to a crowded intracellular environment referred to as molecular crowding. Therefore,...
A two and a half day meeting on G-quadruplexes was held in Louisville, KY, USA (April 18–21, 2009). A specific goal of this conference was to promote discussion on the biology of G-quadruplexes. In practice this was represented in four main ways, namely in biophysics, bio/nanotechnology, therapeutics, and what might be termed “intrinsic biology”. Research into the basic biophysical and structural...
The oncogenic potential of the high-risk human papillomavirus (HPV) relies on the expression of genes specifying the E7 and E6 proteins. To investigate further the variation in oligomeric structure that has been reported for different E7 proteins, an HPV-18 E7 cloned from a Hispanic woman with cervical intraepithelial neoplasia was purified to homogeneity most probably as a stable monomeric protein...
Merozoite surface protein 2 (MSP2) from the human malaria parasite Plasmodium falciparum is expressed as a GPI-anchored protein on the merozoite surface. MSP2 is assumed to have a role in erythrocyte invasion and is a leading vaccine candidate. Recombinant MSP2 forms amyloid-like fibrils upon storage, as do peptides corresponding to sequences in the conserved N-terminal region, which constitutes the...
Hepatitis B virus envelope is mainly composed of three forms of the same protein expressed from different start codons of the same open reading frame. The smaller form named S protein corresponds to the C-terminal common region and represents about 80% of the envelope proteins. It is mainly referred as hepatitis B virus surface antigen (HBsAg). Over expressed in the host cell, this protein can be...
Nep (Natrialba magadii extracellular protease) is a halolysin-like peptidase secreted by the haloalkaliphilic archaeon N. magadii that exhibits optimal activity and stability in salt-saturated solutions. In this work, the effect of salt on the function and structure of Nep was investigated. In absence of salt, Nep became unfolded and aggregated, leading to the loss of activity. The enzyme did not...
The insulin-like growth factor binding proteins are a family of six proteins (IGFBP-1 to -6) that bind insulin-like growth factors-I and -II (IGF-I/II) with high affinity. In addition to regulating IGF actions, IGFBPs have IGF-independent functions. IGFBP-2, the largest member of this family, is over-expressed in many cancers and has been proposed as a possible target for the development of novel...
Hemorrhage is the most potent manifestation of envenomation by Vipera ammodytes ammodytes (V. a. ammodytes) venom in man. A detailed description of the venom components contributing to this effect is thus medically very important. We have characterized a novel component, termed here VaH3, as a potently hemorrhagic snake venom metalloproteinase (SVMP). Its proteolytic activity and overall stability...
NDPK-A, NDPK-B and NDPK-D are three enzymes which belong to the NDPK group I isoforms and are not only involved in metabolism process but also in transcriptional regulation, DNA cleavage, histidine protein kinase activity and metastasis development. Those enzymes were reported to bind to membranes either in mitochondria where NDPK-D influences cardiolipin lateral organization and is thought to be...
Isocitrate lyase (ICL), is a key enzyme of the glyoxylate shunt crucial for the survival of Mycobacterium tuberculosis (Mtb) in macrophages during persistent infection. MtbICL catalyses the first step of this carbon anaplerosis cycle and is considered as a potential anti-tubercular drug target. The MtbICL is a tetramer with 222 symmetry, and each subunit of the enzymeis composed of 14 α-helices and...
Activation of toxin–antitoxin (TA) systems provides an important mechanism for bacteria to adapt to challenging and ever changing environmental conditions. Known TA systems are classified into five families based on the mechanisms of antitoxin inhibition and toxin activity. For type II TA systems, the toxin is inactivated in exponentially growing cells by tightly binding its antitoxin partner protein,...
Lectins are proteins, or glycoproteins, capable of reversibly binding to specific mono- or oligosaccharides via a noncatalytic domain. The Diocleinae subtribe presents lectins with high structural similarity, but different effects based on biological activity assays. This variability results from small structural differences. Therefore, in this context, the present study aimed to perform a structural...
Structural modification of lipid A, the lipid anchor of LPS, is one of the strategies used by Gram-negative bacteria to evade host innate immunity. Francisella tularensis is a human pathogen that infects and replicates within phagocytic cells. It produces an atypical lipid A, whose structure precludes an efficient recognition by both innate immune players, TLR4 and cationic antimicrobial peptides...
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