ORCID Profile
0000-0001-7835-9636
Current Organisation
National Institutes of Health
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Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.PARINT.2012.09.004
Abstract: We identified a shared B domain within nucleoside triphosphate diphosphohydrolases (NTPDases) of plants and parasites. Now, an NTPDase activity not affected by inhibitors of adenylate kinase and ATPases was detected in Leishmania infantum promastigotes. By non-denaturing gel electrophoresis of detergent-homogenized promastigote preparation, an active band hydrolyzing nucleosides di- and triphosphate was visualized and, following SDS-PAGE and silver staining was identified as a single polypeptide of 50kDa. By Western blots, it was recognized by immune sera raised against potato apyrase (SA), r-pot B domain (SB), a recombinant polypeptide derived from the potato apyrase, and LbB1LJ (SC) or LbB2LJ (SD), synthetic peptides derived from the Leishmania NTPDase 1, and by serum s les from dogs with visceral leishmaniasis, identifying the antigenic L. infantum NTPDase 1 and, also, its conserved B domain (r83-122). By immunoprecipitation assays and Western blots, immune sera SA and SB identified the catalytically active NTPDase 1 in promastigote preparation. In addition, the immune sera SB (44%) and SC or SD (87-99%) inhibited its activity, suggesting a direct effect on the B domain. By ELISA, 37%, 45% or 50% of 38 infected dogs were seropositive for r-pot B domain, LbB1LJ and LbB2LJ, respectively, confirming the B domain antigenicity.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0CC90250K
Abstract: Correction for ‘Chemical synthesis of human trefoil factor 1 (TFF1) and its homodimer provides novel insights into their mechanisms of action’ by Nayara Braga Emidio et al. , Chem. Commun. , 2020, DOI: 10.1039/D0CC02321C.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0CC02321C
Abstract: Chemical synthesis of gut peptide TFF1 and its homodimer was achieved by a two-fragment ligation strategy followed by oxidative folding.
Publisher: Elsevier BV
Date: 05-2019
Publisher: American Chemical Society (ACS)
Date: 30-12-2014
DOI: 10.1021/BI400882S
Abstract: α-Conotoxins are competitive antagonists of nicotinic acetylcholine receptors (nAChRs). Their high selectivity and affinity for the various subtypes of nAChRs have led to significant advances in our understanding of the structure and function of these key ion channels. Here we report the discovery of a novel 4/7 α-conotoxin, MrIC from the venom duct of Conus marmoreus, which acts as an agonist at the endogenous human α7 nAChR in SH-SY5Y cells pretreated with PNU120596 (PNU). This unique agonist activity of MrIC at α7 nAChRs may guide the development of novel α7 nAChR modulators.
Publisher: American Chemical Society (ACS)
Date: 09-06-2020
Publisher: MDPI AG
Date: 04-04-2020
DOI: 10.3390/IJMS21072508
Abstract: TFF1 is a protective peptide of the Trefoil Factor Family (TFF), which is co-secreted with the mucin MUC5AC, gastrokine 2 (GKN2), and IgG Fc binding protein (FCGBP) from gastric surface mucous cells. Tff1-deficient mice obligatorily develop antropyloric adenoma and about 30% progress to carcinomas, indicating that Tff1 is a tumor suppressor. As a hallmark, TFF1 contains seven cysteine residues with three disulfide bonds stabilizing the conserved TFF domain. Here, we systematically investigated the molecular forms of TFF1 in the human gastric mucosa. TFF1 mainly occurs in an unusual monomeric form, but also as a homodimer. Furthermore, minor amounts of TFF1 form heterodimers with GKN2, FCGBP, and an unknown partner protein, respectively. TFF1 also binds to the mucin MUC6 in vitro, as shown by overlay assays with synthetic 125I-labeled TFF1 homodimer. The dominant presence of a monomeric form with a free thiol group at Cys-58 is in agreement with previous studies in Xenopus laevis and mouse. Cys-58 is likely highly reactive due to flanking acid residues (PPEEEC58EF) and might act as a scavenger for extracellular reactive oxygen/nitrogen species protecting the gastric mucosa from damage by oxidative stress, e.g., H2O2 generated by dual oxidase (DUOX).
Publisher: American Chemical Society (ACS)
Date: 12-05-2021
Publisher: Springer Science and Business Media LLC
Date: 07-10-2020
Publisher: China Science Publishing & Media Ltd.
Date: 06-2017
DOI: 10.1093/ABBS/GMX031
Publisher: American Chemical Society (ACS)
Date: 14-04-2022
Publisher: American Chemical Society (ACS)
Date: 06-10-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2CC03752A
Abstract: Regiospecific incorporation of a protected aminooxy group into disulfide-rich peptides compatible with oxidative folding. This strategy supports the production of aminooxy precursors for long-term storage and on-demand modifications.
Publisher: American Chemical Society (ACS)
Date: 20-10-2020
Publisher: Cold Spring Harbor Laboratory
Date: 30-07-2020
DOI: 10.1101/2020.07.29.226878
Abstract: Ants use venom for predation, defence and communication, however, the molecular ersity, function and potential applications of ant venom remains understudied compared to other venomous lineages such as arachnids, snakes and cone snails. In this work, we used a multidisciplinary approach that encompassed field work, proteomics, sequencing, chemical synthesis, structural analysis, molecular modelling, stability studies, and a series of in vitro and in vivo bioassays to investigate the molecular ersity of the venom of the Amazonian Pseudomyrmex penetrator ants. We isolated a potent insecticidal heterodimeric peptide Δ-pseudomyrmecitoxin-Pp1a (Δ-PSDTX-Pp1a) composed of a 27-residue long A-chain and a 33-residue long B-chain crosslinked by two disulfide bonds in an antiparallel orientation. We chemically synthesised Δ-PSDTX-Pp1a, its corresponding parallel AA and BB homodimers, and its monomeric chains and demonstrated that Δ-PSDTX-Pp1a had the most potent insecticidal effects in blow fly assays (LD 50 = 3 nM). Molecular modelling and circular dichroism studies revealed strong alpha-helical features, indicating its cytotoxic effects could derive from membrane disruption, which was further supported by insect cell calcium assays. The native heterodimer was also substantially more stable against proteolytic degradation (t 1/2 =13 h) than its homodimers or monomers (t 1/2 min), indicating an evolutionary advantage of the more complex structure. The proteomic analysis of Pseudomyrmex penetrator venom and in-depth characterisation of Δ-PSDTX-Pp1a provide novel insights in the structural complexity of ant venom, and further exemplifies how nature exploits disulfide-bond formation and dimerization to gain an evolutionary advantage via improved stability a concept that is also highly relevant for the design and development of peptide therapeutics, molecular probes and bioinsecticides.
Publisher: American Chemical Society (ACS)
Date: 18-06-2021
Publisher: Cold Spring Harbor Laboratory
Date: 08-10-2023
Publisher: MDPI AG
Date: 26-01-2021
DOI: 10.3390/MD19020060
Abstract: Conotoxins are disulfide-rich peptides found in the venom of cone snails. Due to their exquisite potency and high selectivity for a wide range of voltage and ligand gated ion channels they are attractive drug leads in neuropharmacology. Recently, cone snails were found to have the capability to rapidly switch between venom types with different proteome profiles in response to predatory or defensive stimuli. A novel conotoxin, GXIA (original name G117), belonging to the I3-subfamily was identified as the major component of the predatory venom of piscivorous Conus geographus. Using 2D solution NMR spectroscopy techniques, we resolved the 3D structure for GXIA, the first structure reported for the I3-subfamily and framework XI family. The 32 amino acid peptide is comprised of eight cysteine residues with the resultant disulfide connectivity forming an ICK+1 motif. With a triple stranded β-sheet, the GXIA backbone shows striking similarity to several tarantula toxins targeting the voltage sensor of voltage gated potassium and sodium channels. Supported by an hipathic surface, the structural evidence suggests that GXIA is able to embed in the membrane and bind to the voltage sensor domain of a putative ion channel target.
No related grants have been discovered for Nayara Braga Emidio.