Systems used to automatically annotate proteins with high accuracy:.
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Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours
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Your basket is currently empty. Submitted name: Prohormone and neuropeptide processing protease. Drosophila melanogaster Fruit fly. Select a section on the left to see content. Insect cell-specific processing and secretion. PLoS Genet. Proteome Res. GO - Cellular component Extracellular region or secreted extracellular region Source: FlyBase Inferred from direct assay i "Interaction of Drosophila melanogaster prohormone convertase 2 and 7B2. Bgee i FBgn Expressed in 22 organ s , highest expression level in brain. The information is filed in different subsections.
Length: Mass Da : 71, It is useful for tracking sequence updates. The algorithm is described in the ISO standard. Full view.
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- Genetic Programming: 13th European Conference, EuroGP 2010, Istanbul, Turkey, April 7-9, 2010. Proceedings;
- Methods in Neurosciences: Peptidases and Neuropeptide Processing?
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- Prohormone and neuropeptide processing protease!
- Kinetic Study of Neuropeptide Y (NPY) Proteolysis in Blood and Identification of NPY3–35.
Caenorhabditis nigoni. These are stable identifiers and should be used to cite UniProtKB entries. See complete history. Previous results from our group showed that the metallopeptidases present in this venom are capable of hydrolyzing the neuropeptide dynorphin in vitro , releasing Leu-enkephalin, which may interact with ion channels and promote indirect neurotoxicity.
Thus, this study aims to get more information about the effect of toxic peptidase activity present in the venom on biologically active peptides, and to evaluate the in vitro neutralizing potential of commercial antivenoms produced by the Butantan Institute. A set of human bioactive peptides were studied as substrates for the peptidases, and the members of the neuropeptide Y family were found to be the most susceptible ones.
All new substrate hydrolyses were totally inhibited by ethylenediaminetetracetic and not blocked by phenylmethanesulfonylfluoride, indicating that metallopeptidases were responsible for the peptidase activity. These characterizations, unpublished until now, can contribute to the improvement of our knowledge about the venom and envenomation processes by T.
The increasing number of accidents involving scorpions in Brazil led us to develop this study because, since scorpionism is the major cause of human envenomation by animals in this country, surpassing accidents with snakes and spiders. Most of the critical clinical cases are attributed to envenomation with Tityus serrulatus scorpions, and there are two major reasons for that; the first one is its ability to adapt to densely populated areas also based on its parthenogenetic reproduction ; second is the potential of its venom to induce severe clinical manifestations, becoming potentially fatal among children and elders.
The T. The neurotoxins action in the CNS is especially important in cases of envenomation involving children, as the blood-brain barrier is permeable enough to allow venom penetration Guidine et al. Some of the symptoms displayed by victims of scorpion envenomation are: fever, restlessness, excessive salivation, lacrimation, increased gastrointestinal motility, respiratory, and cardiac arrhythmias, acute pulmonary inflammation, and hypertension followed by hypotension, heart failure, and cardiogenic shock.
In part, these clinical manifestations may be explained by the presence of neurotoxic components in the venom, which interact with sodium and potassium channels in nerve endings Warnick et al. The first and only metallopeptidase that was purified from the venom of T. Antarease is a single-chain molecule composed of residues with a molecular mass of Fletcher et al.
In this study, the authors showed that antarease can cleave Soluble N-ethylmaleimide-sensitive factor Attachment protein Receptors SNARE proteins within exocrine pancreatic tissue. The toxicological effects of scorpion venoms have been assigned to several non-peptidase components, such as ion-channel active peptides and hyaluronidases.
However, with the recent elucidation of the presence of peptidases on these venoms, they have become increasingly evident as an important function of peptide-metabolizing enzymes to generate new peptides with different biological activities Carvalho et al.
Although studies seek mainly proteins as substrates, bioactive peptides should be considered as important targets during the envenomation. In this way, toxic peptidases have the potential ability to act upon bioactive peptides to modulate blood pressure, pain sensation, glycemic control, and emotional behavior, and to increase the permeability of the target cells to venom toxins, which are known effects of T.
Recently our group was able to identify a new dynorphin 1—13 degrading activity with releasing of Leu-enkephalin in the T. Dynorphin 1—13 is a endogenous opioid peptide that is involved in physiological processes such as antinociceptive and neuroendocrine signaling. However, the injection of higher doses of this peptide in rats results in the increase of cytotoxicity, generating neuropathic pain Venancio et al. These results, describing a new metallopeptidase activity in TsV, gave us an opportunity to extend the studies using other biologically active peptides, which may be participating in the framework of human envenomation by these animals.
Based on that, we investigated possible new substrates with a set of biologically active peptides and checked the neutralization of the two commercial antivenoms produced by the Butantan Institute against the metallopeptidases of TsV, the most predominant toxic peptidases of this venom Verano-Braga et al. Acetonitrile and trifluoroacetic acid TFA from J. The lyophilized venom of T. The SAV batch no. The antivenoms from the Butantan Institute are produced through the hyperimmunization of horses with a pool of venoms containing T.
This assay was executed according to Smith et al. The enzymatic activity of the T. When necessary, control samples were prepared in the presence of an equal volume of ethanol, which was used in the PMSF stock solutions. The concentrations of the peptides used were predetermined to yield measures of maximum velocities Vmax of the reactions data not shown.
All assays were performed in duplicate. The peaks were manually collected and scissile bonds determined by mass spectrometric analyses. The HPLC-fractions resulting from the isolation of fragments generated by the hydrolysis of bioactive peptides by TsV were resuspended in 0. The spectrometer was operated in data-dependent mode and the 10 most intense peaks were selected for CID fragmentation after acquiring each full scan. A decoy database was also searched to calculate false discovery rate FDR using the decoy-fusion method Ma et al. The ability of the antivenoms to neutralize the peptidase activity of the venom was estimated as previously described Kuniyoshi et al.
First, we performed a serum neutralization assay of TsV activity upon the FRET substrate using different doses of the antivenoms. Also, we determined the ability of the commercial antivenoms to neutralize the hydrolysis of bioactive peptides by TsV using reverse phase chromatography. Doses below did not show inhibition and are not shown. The result is expressed as the inhibition of the peptidase activity of the venoms percent. Experiments were made in triplicate.
The bioactive peptides neurotensin, somatostatin, angiotensin I, and bradykinin were not hydrolyzed by the TsV, even after overnight incubations. The results are expressed in Table 2.
nEUROSTRESSPEP: Insect Neuropeptides
The products of hydrolysis varied on the quantity—hemopressin 5 fragments ; PYY 23 fragments ; NPY 40 fragments ; PP 31 fragments —and also in length, presenting bigger, medium, and smaller fragments e. In terms of similarity, it is noteworthy that Tyr 36 -NH 2 was not present in any of the fragments from the NPY family of peptides. As demonstrated in Figure 1 panel B , the AAV shows partial neutralization activity on early doses from dose of weight ratio of venom:antivenom , whereas SAV only starts to block the activity after the dose. We also evaluated the neutralization ability of AAV and SAV to block the hydrolysis over the bioactive peptides that were substrates by TsV using reverse-phase chromatography.
However, the hydrolysis of hemopressin did not present a dose-dependent pattern and this activity was not inhibited by the times higher dose of SAV. Controls with peptides and the antivenoms were made and no hydrolyses were observed data not shown. Neutralization of Tityus serrulatus venom TsV peptidases by the commercial antivenoms over biologically active peptides. The result is expressed as the inhibition of the peptidase activity of the venom percent. The large amount of fragments produced by the action of the venom upon the peptides used in this study reveals that the endopeptidases and exopeptidases are present in the TsV.
However, there is no clear specificity for the generation of fragments observed.