Novel conopeptides of the I-superfamily occur in several clades of cone snails

The I-superfamily of conotoxins represents a new class of peptides in the venom of some Conus species. These toxins are characterized by four disulfide bridges and inhibit or modify ion channels of nerve cells. When testing venoms from 11 Conus species for a functional characterization, blocking activity on potassium channels (like Kv1.1 and Kv1.3 channels, but not Kv1.2 channels) was detected in the venom of Conus capitaneus, Conus miles, Conus vexillum and Conus virgo. Analysis at the cDNA level of these venoms using primers designed according to the amino acid sequence of a potassium channel blocking toxin (ViTx) from C. virgo confirmed the presence of structurally homologous peptides in these venoms. Moreover, peptides belonging to the I-superfamily, but with divergent amino acid sequences, were found in Conus striatus and Conus imperialis. In all cases, the sequences of the precursors' prepro-regions exhibited high conservation, whereas the sequences of the mature peptides ranged from almost identical to highly divergent between species. We then performed phylogenetic analyses of new and published mitochondrial 16S rDNA sequences representing 104 haplotypes from these and numerous other Conus species, using Bayesian, maximum-likelihood, maximum-parsimony and neighbor-joining methods of inference. Cone snails known to possess I-superfamily toxins were assigned to five different major clades in all of the resulting gene trees. Moreover, I-superfamily conopeptides were detected both in vermivorous and piscivorous species of Conus, thus demonstrating the widespread presence of such toxins in this speciose genus beyond evolutionary and ecological groups

Primary structure and electrophysiological characterization of two almost identical isoforms of toxin from Isometrus vittatus (family: Buthidae) scorpion venom.

Two almost identical proteins with 70 amino acid residues each, closely packed by four disufide bridges, and molecular masses of 7899.5 and 7884.7 were isolated and sequenced from the venom of the scorpion Isometrus vittatus from Pakistan. They differ by an acidic amino acid residue (glutamic or aspartic) at the same position 55 of the peptide chain, however, they exhibit the same length, the same charge and are undistinguishable when separated by C(18) reverse phase HPLC. The mixture of the two proteins called IsomTx1 depolarizes the cockroach isolated axon; artificial repolarization is followed by sustained repetitive activity, artificial hyperpolarization facilitates bursting activity observed as an answer to rapid depolarization to -60 mV. The depolarization is antagonized by TTX. In voltage-clamp experiments IsomTx1 increases axonal sodium permeability which has a particular importance between resting and threshold potentials and moderately slows down the fast inactivation. These characteristics closely resemble those of other anti-insect scorpion toxins classified as contractive toxins from Androctonus and Buthotus venoms

Oxygen Evolution Activity of Amorphous Cobalt Oxyhydroxides Interconnecting Precatalyst Reconstruction, Long Range Order, Buffer Binding, Morphology, Mass Transport, and Operation Temperature

Nanocrystalline or amorphous cobalt oxyhydroxides CoCat are promising electrocatalysts for the oxygen evolution reaction OER . While having the same short range order, CoCat phases possess different electrocatalytic properties. This phenomenon is not conclusively understood, as multiple interdependent parameters affect the OER activity simultaneously. Herein, a layered cobalt borophosphate precatalyst, Co H2O 2[B2P2O8 OH 2] H2O, is fully reconstructed into two different CoCat phases. In contrast to previous reports, this reconstruction is not initiated at the surface but at the electrode substrate to catalyst interface. Ex situ and in situ investigations of the two borophosphate derived CoCats, as well as the prominent CoPi and CoBi identify differences in the Tafel slope range, buffer binding and content, long range order, number of accessible edge sites, redox activity, and morphology. Considering and interconnecting these aspects together with proton mass transport limitations, a comprehensive picture is provided explaining the different OER activities. The most decisive factors are the buffers used for reconstruction, the number of edge sites that are not inhibited by irreversibly bonded buffers, and the morphology. With this acquired knowledge, an optimized OER system is realized operating in near neutral potassium borate medium at 1.62 0.03 VRHE yielding 250 mA cm amp; 8722;2 at 65 C for 1 month without degrading performanc

Synthesis and Single-Electron Oxidation of Bulky Bis(m-terphenyl)chalcogenides: The Quest for Kinetically Stabilized Radical Cations

Sterically encumbered bis(m-terphenyl)chalcogenides, (2,6-Mes2C6H3)2E (E=S, Se, Te) were obtained by the reaction of the chalcogen tetrafluorides, EF4, with three equivalents of m-terphenyl lithium, 2,6-Mes2C6H3Li. The single-electron oxidation of (2,6-Mes2C6H3)2Te using XeF2/K[B(C6F5)4] afforded the radical cation [(2,6-Mes2C6H3)2Te][B(C6F5)4] that was isolated and fully characterized. The electrochemical oxidation of the lighter homologs (2,6-Mes2C6H3)2E (E=S, Se) was irreversible and impaired by rapid decomposition

Spectroscopic Properties of a Biologically Relevant [Fe2(μ-O)2] Diamond Core Motif with a Short Iron-Iron Distance

Diiron cofactors in enzymes perform diverse challenging transformations. The structures of high valent intermediates (Q in methane monooxygenase and X in ribonucleotide reductase) are debated since Fe−Fe distances of 2.5–3.4 Å were attributed to “open” or “closed” cores with bridging or terminal oxido groups. We report the crystallographic and spectroscopic characterization of a FeIII2(μ-O)2 complex (2) with tetrahedral (4C) centres and short Fe−Fe distance (2.52 Å), persisting in organic solutions. 2 shows a large Fe K-pre-edge intensity, which is caused by the pronounced asymmetry at the TD FeIII centres due to the short Fe−μ−O bonds. A ≈2.5 Å Fe−Fe distance is unlikely for six-coordinate sites in Q or X, but for a Fe2(μ-O)2 core containing four-coordinate (or by possible extension five-coordinate) iron centres there may be enough flexibility to accommodate a particularly short Fe−Fe separation with intense pre-edge transition. This finding may broaden the scope of models considered for the structure of high-valent diiron intermediates formed upon O2 activation in biology

Evidence of Sulfur Non-Innocence in [CoII(dithiacyclam)]2+-Mediated Catalytic Oxygen Reduction Reactions

In many metalloenzymes, sulfur-containing ligands participate in catalytic processes, mainly via the involvement in electron transfer reactions. In a biomimetic approach, we now demonstrate the implication of S-ligation in cobalt mediated oxygen reduction reactions (ORR). A comparative study between the catalytic ORR capabilities of the four-nitrogen bound [Co(cyclam)]2+ (1; cyclam=1,5,8,11-tetraaza-cyclotetradecane) and the S-containing analog [Co(S2N2-cyclam)]2+ (2; S2N2-cyclam=1,8-dithia-5,11-diaza-cyclotetradecane) reveals improved catalytic performance once the chalcogen is introduced in the Co coordination sphere. Trapping and characterization of the intermediates formed upon dioxygen activation at the CoII centers in 1 and 2 point to the involvement of sulfur in the O2 reduction process as the key for the improved catalytic ORR capabilities of 2

Operando tracking of oxidation-state changes by coupling electrochemistry with time-resolved X-ray absorption spectroscopy demonstrated for water oxidation by a cobalt-based catalyst film

Transition metal oxides are promising electrocatalysts for water oxidation, i.e., the oxygen evolution reaction (OER), which is critical in electrochemical production of non-fossil fuels. The involvement of oxidation state changes of the metal in OER electrocatalysis is increasingly recognized in the literature. Tracing these oxidation states under operation conditions could provide relevant information for performance optimization and development of durable catalysts, but further methodical developments are needed. Here, we propose a strategy to use single-energy X-ray absorption spectroscopy for monitoring metal oxidation-state changes during OER operation with millisecond time resolution. The procedure to obtain time-resolved oxidation state values, using two calibration curves, is explained in detail. We demonstrate the significance of this approach as well as possible sources of data misinterpretation. We conclude that the combination of X-ray absorption spectroscopy with electrochemical techniques allows us to investigate the kinetics of redox transitions and to distinguish the catalytic current from the redox current. Tracking of the oxidation state changes of Co ions in electrodeposited oxide films during cyclic voltammetry in neutral pH electrolyte serves as a proof of principle

Novel long-chain neurotoxins from Bungarus candidus distinguish the two binding sites in muscle-type nicotinic acetylcholine receptors

αδ-Bungarotoxins, a novel group of long-chain α-neurotoxins, manifest different affinity to two agonist/competitive antagonist binding sites of muscle-type nicotinic acetylcholine receptors (nAChRs), being more active at the interface of α–δ subunits. Three isoforms (αδ-BgTx-1–3) were identified in Malayan Krait (Bungarus candidus) from Thailand by genomic DNA analysis; two of them (αδ-BgTx-1 and 2) were isolated from its venom. The toxins comprise 73 amino acid residues and 5 disulfide bridges, being homologous to α-bungarotoxin (α-BgTx), a classical blocker of muscle-type and neuronal α7, α8, and α9α10 nAChRs. The toxicity of αδ-BgTx-1 (LD50 = 0.17–0.28 µg/g mouse, i.p. injection) is essentially as high as that of α-BgTx. In the chick biventer cervicis nerve–muscle preparation, αδ-BgTx-1 completely abolished acetylcholine response, but in contrast with the block by α-BgTx, acetylcholine response was fully reversible by washing. αδ-BgTxs, similar to α-BgTx, bind with high affinity to α7 and muscle-type nAChRs. However, the major difference of αδ-BgTxs from α-BgTx and other naturally occurring α-neurotoxins is that αδ-BgTxs discriminate the two binding sites in the Torpedo californica and mouse muscle nAChRs showing up to two orders of magnitude higher affinity for the α–δ site as compared with α–ε or α–γ binding site interfaces. Molecular modeling and analysis of the literature provided possible explanations for these differences in binding mode; one of the probable reasons being the lower content of positively charged residues in αδ-BgTxs. Thus, αδ-BgTxs are new tools for studies on nAChRs

Spektroskopische Eigenschaften eines biologisch relevanten [Fe2 mu O 2] Diamond Core Motivs mit einem kurzen Eisen Eisen Abstand

Dieisen Kofaktoren in Enzymen vollziehen diverse anspruchsvolle Transformationen. Die Strukturen hoch valenter Intermediate Q in der löslichen Methanmonooxygenase und X in der Ribonukleotidreduktase sind Gegenstand aktueller Diskussionen, seit Fe Fe Abstände von 2.1 3.4 amp; 8197; eine Zuordnung zu geöffneten und geschlossen Kernen mit verbrückenden oder terminalen Oxido Gruppen in den aktiven Zentren ermöglichen. In dieser Studie berichten wir die kristallografische und spektroskopische Charakterisierung eines FeIII2 amp; 956; O 2 Komplexes 2 mit tetraedrischen 4C Zentren sowie einem geringen Fe Fe Abstand 2.52 amp; 8197; , der in Lösungsmitteln beständig ist. 2 zeigt eine gro e Fe K Vorkanten Intensität. Diese resultiert aus der starken Asymmetrie an den TD FeIII Zentren bedingt durch die kurzen Fe amp; 956; O Bindungen. Während ein Fe Fe Abstand von amp; 8776;2.5 amp; 8197; für sechsfach koordinierte Zentren in Q und X unwahrscheinlich ist, könnte ein Fe2 amp; 956; O 2 Kern mit vierfacher oder möglicherweise auch fünffacher Koordination flexibel genug sein, um eine kurze Fe Fe Separierung mit gro er Vorkanten Intensität zu ermöglichen. Diese Erkenntnis kann dazu beitragen, dass weitere Modelle für die Strukturen der hoch valenten Dieisen Intermediate, die sich im Zuge der biologischen O2 Aktivierung bilden, in Betracht gezogen werde