Isolation and Characterization of a Peptide Isomerase from Funnel Web Spider Venom

Shikata, Yasushi; Watanabe, Tomohiro; Teramoto, Takashi; Inoue, Atsushi; Kawakami, Yoshiyuki; Nishizawa, Yuji; Katayama, Kouichi; Kuwada, Manabu

doi:10.1074/jbc.270.28.16719

Cited by 96 publications

(64 citation statements)

References 15 publications

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“…5A) or with a mixture of 1 ,uM w-conotoxin MVIIC, 1 ,iiM w-conotoxin GVIA, and 0.2 ,iiM agatoxin TK (Fig. 6A), confirming that the depolarization-induced increases in [Ca2~I, resulted from the opening of voltage-gated Ca2~channels (Nachshen and Blaustein, 1979;Dunlap et al, 1995) largely belonging to the N-, P-, and Qtype family of channels in view of the selectivity of the toxins used (Rivier et al, 1987;Hillyard et al, 1992;Shikata et al, 1995). (In preliminary experiments, we tested a broad variety of Ca2~channel toxin combinations and found that the mixture used in the present study was the most effective in blocking K ±-induced changes in [Ca2~]~in striatal synaptosomes.)…”

Section: Determination Of Pathway For Ca 2~entry On Activation Of Synmentioning

confidence: 56%

High Calcium Permeability of Serotonin 5‐HT₃ Receptors on Presynaptic Nerve Terminals from Rat Striatum

Rondé

Nichols

1998

Journal of Neurochemistry

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Abstract:The serotonin 5-HT3 receptor, a ligand-gated ion channel, has previously been shown to be present on a subpopulation of brain nerve terminals, where, on activation, the 5-HT3 receptors induce Ca 2~influx. Whereas postsynaptic 5-HT 3 receptors induce depolarization, being permeant to Naãnd K~, the basis of presynaptic 5-HT3 receptor-induced calcium influx is unknown. Because the small size of isolated brain nerve terminals (synaptosomes) precludes electrophysiological measurements, confocal microscopic imaging has been used to detect calcium influx into them. Application of 100 n M 1-(m-chlorophenyl) biguanide (mCPBG), a highly specific 5-HT3 receptor agonist, induced increases in internal free Ca 2~concentration ([Ca2~]) and exocytosis in a subset of corpus striatal synaptosomes. mCPBG-induced increases in [Ca2~]ranged from 1.3 to 1 .6 times over basal values and were inhibited by 10 nM tropisetron, a potent and highly specific 5-HT 3 receptor antagonist, but were insensitive to the removal of external free Na~(substituted with N-methyl-o-glucamine), to prior depolarization induced on addition of 20 mM K~, or to voltage-gated Ca 2~channel blockade by 10 p~M Co2~/Cd2õrbyl ,uMw-conotoxin MVIIC/1~tMw-conotoxin GVIA/200 nM agatoxin TK. In contrast, the Ca2ĩ nflux induced by 5-HT 3 receptor activation in NG1 08-15 cells by 1 ,tiM mCPBG was substantially reduced by 10.tMCo 2~/Cd2ãnd was completely blocked by 1 ,uM nitrendipine, an L-type Ca2~channel blocker. We conclude that in contrast to the perikaryal 5-HT 3 receptors, presynaptic 5-HT3 receptors appear to be uniquely calcium-permeant. Key Words: Serotonin 5-HT3 receptorPresynaptic regulation-Synaptosomes-Confocal microscopy-Internal free Ca 2~concentration measurements-NG1O8-15 cells.

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Section: Determination Of Pathway For Ca 2~entry On Activation Of Synmentioning

confidence: 56%

High Calcium Permeability of Serotonin 5‐HT₃ Receptors on Presynaptic Nerve Terminals from Rat Striatum

Rondé

Nichols

1998

Journal of Neurochemistry

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“…The mRNA of D/Lpeptides contains codons for L-amino acids and isomerization of one of these amino acids is catalyzed post-translation by specific peptide L/D-isomerases (Bansal et al, 2008;Heck et al, 1996;Jilek et al, 2005;Shikata et al, 1995). This apparently uncommon chirality was revealed in a variety of taxa, reviewed by Kreil (Kreil, 1997) and summarized by Buczek et al (Buczek et al, 2005) and Ollivaux et al (Ollivaux et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Different transcription regulation routes are exerted by L- and D-amino acid enantiomers of peptide hormones

Tom

Manfrin

Mosco

et al. 2014

Journal of Experimental Biology

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Conversion of one or more amino acids in eukaryotic peptides to the D-enantiomer configuration is catalyzed by specific L/D-peptide isomerases and it is a poorly investigated post-translational modification. No common modified amino acid or specific modified position has been recognized, and mechanisms underlying changes in the peptide function provided by this conversion are not widely studied. The 72 amino acid crustacean hyperglycemic hormone (CHH) in Astacidea crustaceans exhibits a co-existence of two peptide enantiomers with either D-or L-phenylalanine as their third residue. It is a pleiotropic hormone regulating several physiological processes in different target tissues and along different time scales. CHH enantiomers differently affect time courses and intensities of examined processes. The short-term effects of the two isomers on gene expression were examined in the hepatopancreas, gills, hemocytes and muscles of the astacid Pontastacus leptodactylus. Gene expression in muscles and hemocytes was not affected by either of the isomers. Two modes of action for CHH were elucidated in the hepatopancreas and the gills: specific gene induction in both organs by D-CHH, and targeted attenuation caused by both enantiomers in the gills. Consequently, a two-receptor system is proposed for conveying the effect of the two CHH isomers.

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“…For example, the enzyme from Conus snails that catalyzes the vitamin K-dependent formation of the ␥-carboxy glutamic acids present in some venom peptides is highly homologous to the corresponding carboxylase from bovine liver (28,29). Thus, it seems to be surprising that structurally unrelated enzymes catalyze the L-D-isomerization of amino acids in peptide linkage in spider venom (15) and frogs. Evidence indicates that, in both cases, the catalytic mechanism is basically the same (namely, removal of a proton from the ␣-carbon and concomitant addition from the opposite side in an acid-base type of catalysis).…”

Section: Discussionmentioning

confidence: 99%

“…In this case, the chirality of a Ser close to the C terminus of a peptide termed -agatoxin IV is inverted. This ''isomerase'' is related to Ser proteases and functions without any added cofactors (14,15).…”

mentioning

confidence: 99%

Biosynthesis of a D-amino acid in peptide linkage by an enzyme from frog skin secretions

Jilek

Mollay

Tippelt

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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D-amino acids are present in some peptides from amphibian skin. These residues are derived from the corresponding L-amino acids present in the respective precursors. From skin secretions of Bombinae, we have isolated an enzyme that catalyzes the isomerization of an L-Ile in position 2 of a model peptide to D-allo-Ile. In the course of this reaction, which proceeds without the addition of a cofactor, radioactivity from tritiated water is incorporated into the second position of the product. The amino acid sequence of this isomerase could be deduced from cloned cDNA and genomic DNA. After expression of this cDNA in oocytes of Xenopus laevis, isomerase activity could be detected. Polypeptides related to the frog skin enzyme are present in several vertebrate species, including humans.amphibia ͉ bombinin H ͉ isomerase ͉ chirality F rom amphibian skin, a wide variety of biologically active peptides have been isolated (1). One of these compounds, the heptapeptide dermorphin (present in the skin of the South American tree frog Phyllomedusa sauvagei), is a potent opiate that binds with high affinity and selectivity to -opiate receptors (2). Quite unexpectedly, dermorphin was found to contain D-Ala at position 2, and this residue is essential for binding to the receptor. Subsequently, several additional opiate peptides containing a D-amino acid were found in the skin of other Phyllomedusinae (3). The bombinins H, antibacterial and hemolytic peptides isolated from skin secretions of the frog Bombina variegata, contain either L-Ile or D-allo-Ile (D-aIle) as the second amino acid (4). Peptides with D-amino acids in their sequences were also found in different invertebrate species, such as snails (5-7), the venom of a spider (8), and crustaceans (9). The most recent addition to this group was a homologue of C-type natriuretic peptides isolated from the venom of the male platypus (10).In principle, the biosynthesis of these D-amino acids in animal peptides has been clarified. As shown for dermorphin (11) and subsequently for several cases of vertebrate and invertebrate peptides, the secreted products are derived from larger precursors encoded by mRNAs. At the positions where a D-amino acid is present in the end product, a codon for the corresponding L-isomer has been found (reviewed in refs. 12 and 13). This finding implies that, at some stage in the processing of the precursors, a conversion of certain L-amino acids to the D-form takes place. Indeed, in many cases, the L and D forms of the mature peptides coexist in the respective secretory glands and secretions, which can be interpreted as incomplete isomerization. An enzyme that catalyzes such an unusual reaction has been characterized from the venom of a funnel web spider (8). In this case, the chirality of a Ser close to the C terminus of a peptide termed -agatoxin IV is inverted. This ''isomerase'' is related to Ser proteases and functions without any added cofactors (14, 15).As mentioned above, skin secretions of Bombina species contain a group of hemolytic peptides tha...

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Isolation and Characterization of a Peptide Isomerase from Funnel Web Spider Venom

Cited by 96 publications

References 15 publications

High Calcium Permeability of Serotonin 5‐HT₃ Receptors on Presynaptic Nerve Terminals from Rat Striatum

High Calcium Permeability of Serotonin 5‐HT₃ Receptors on Presynaptic Nerve Terminals from Rat Striatum

Different transcription regulation routes are exerted by L- and D-amino acid enantiomers of peptide hormones

Biosynthesis of a D-amino acid in peptide linkage by an enzyme from frog skin secretions

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Isolation and Characterization of a Peptide Isomerase from Funnel Web Spider Venom

Cited by 96 publications

References 15 publications

High Calcium Permeability of Serotonin 5‐HT3 Receptors on Presynaptic Nerve Terminals from Rat Striatum

High Calcium Permeability of Serotonin 5‐HT3 Receptors on Presynaptic Nerve Terminals from Rat Striatum

Different transcription regulation routes are exerted by L- and D-amino acid enantiomers of peptide hormones

Biosynthesis of a D-amino acid in peptide linkage by an enzyme from frog skin secretions

Contact Info

Product

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High Calcium Permeability of Serotonin 5‐HT₃ Receptors on Presynaptic Nerve Terminals from Rat Striatum

High Calcium Permeability of Serotonin 5‐HT₃ Receptors on Presynaptic Nerve Terminals from Rat Striatum