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1.
Toxins (Basel) ; 13(6)2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201318

RESUMO

The Colombian scorpion Centruroides margaritatus produces a venom considered of low toxicity. Nevertheless, there are known cases of envenomation resulting in cardiovascular disorders, probably due to venom components that target ion channels. Among them, the humanether-à-go-go-Related gene (hERG1) potassium channels are critical for cardiac action potential repolarization and alteration in its functionality are associated with cardiac disorders. This work describes the purification and electrophysiological characterization of a Centruroides margaritatus venom component acting on hERG1 channels, the CmERG1 toxin. This novel peptide is composed of 42 amino acids with a MW of 4792.88 Da, folded by four disulfide bonds and it is classified as member number 10 of the γ-KTx1 toxin family. CmERG1 inhibits hERG1 currents with an IC50 of 3.4 ± 0.2 nM. Despite its 90.5% identity with toxin É£-KTx1.1, isolated from Centruroides noxius, CmERG1 completely blocks hERG1 current, suggesting a more stable plug of the hERG channel, compared to that formed by other É£-KTx.


Assuntos
Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Peptídeos/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Venenos de Escorpião/farmacologia , Animais , Colômbia , Canais de Potássio Éter-A-Go-Go/fisiologia , Peptídeos/isolamento & purificação , Bloqueadores dos Canais de Potássio/isolamento & purificação , Venenos de Escorpião/isolamento & purificação , Escorpiões
2.
Toxicon ; 119: 253-65, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27349167

RESUMO

Potassium (K(+)) channels are trans-membrane proteins, which play a key role in cellular excitability and signal transduction pathways. Scorpion toxins blocking the ion-conducting pore from the external side have been invaluable probes to elucidate the structural, functional, and physio-pathological characteristics of these ion channels. This review will focus on the interaction between K(+) channels and their peptide blockers isolated from the venom of the scorpion Tityus serrulatus, which is considered as the most dangerous scorpion in Brazil, in particular in Minas-Gerais State, where many casualties are described each year. The primary mechanisms of action of these K(+) blockers will be discussed in correlation with their structure, very often non-canonical compared to those of other well known K(+) channels blockers purified from other scorpion venoms. Also, special attention will be brought to the most recent data obtained by proteomic and transcriptomic analyses on Tityus serrulatus venoms and venom glands.


Assuntos
Bloqueadores dos Canais de Potássio/isolamento & purificação , Venenos de Escorpião/química , Toxinas Biológicas/isolamento & purificação , Sequência de Aminoácidos , Animais , Modelos Moleculares , Bloqueadores dos Canais de Potássio/química , Bloqueadores dos Canais de Potássio/toxicidade , Espectroscopia de Prótons por Ressonância Magnética , Homologia de Sequência de Aminoácidos , Toxinas Biológicas/química , Toxinas Biológicas/toxicidade
3.
Toxicon ; 115: 1-12, 2016 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-26921461

RESUMO

Six new peptides were isolated from the venom of the Mexican scorpion Centruroides tecomanus; their primary structures were determined and the effects on ion channels were verified by patch-clamp experiments. Four are K(+)-channel blockers of the α-KTx family, containing 32 to 39 amino acid residues, cross-linked by three disulfide bonds. They all block Kv1.2 in nanomolar concentrations and show various degree of selectivity over Kv1.1, Kv1.3, Shaker and KCa3.1 channels. One peptide has 42 amino acids cross-linked by four disulfides; it blocks ERG-channels and belongs to the γ-KTx family. The sixth peptide has only 32 amino acid residues, three disulfide bonds and has no effect on the ion-channels assayed. It also does not have antimicrobial activity. Systematic numbers were assigned (time of elution on HPLC): α-KTx 10.4 (time 24.1); α-KTx 2.15 (time 26.2); α-KTx 2.16 (time 23.8); α-KTx 2.17 (time 26.7) and γ-KTx 1.9 (elution time 29.6). A partial proteomic analysis of the short chain basic peptides of this venom, which elutes on carboxy-methyl-cellulose column fractionation, is included. The pharmacological properties of the peptides described in this study may provide valuable tools for understanding the structure-function relationship of K(+) channel blocking scorpion toxins.


Assuntos
Bloqueadores dos Canais de Potássio/química , Venenos de Escorpião/química , Escorpiões , Sequência de Aminoácidos , Animais , Linhagem Celular , Fenômenos Eletrofisiológicos , Humanos , México , Testes de Sensibilidade Microbiana , Peptídeos/química , Peptídeos/isolamento & purificação , Peptídeos/farmacologia , Bloqueadores dos Canais de Potássio/isolamento & purificação , Bloqueadores dos Canais de Potássio/farmacologia , Proteômica , Venenos de Escorpião/farmacologia
4.
Toxicon ; 93: 125-35, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25432067

RESUMO

Scorpions are well known for their dangerous stings that can result in severe consequences for human beings, including death. Neurotoxins present in their venoms are responsible for their toxicity. Due to their medical relevance, toxins have been the driving force in the scorpion natural compounds research field. On the other hand, for thousands of years, scorpions and their venoms have been applied in traditional medicine, mainly in Asia and Africa. With the remarkable growth in the number of characterized scorpion venom components, several drug candidates have been found with the potential to tackle many of the emerging global medical threats. Scorpions have become a valuable source of biologically active molecules, from novel antibiotics to potential anticancer therapeutics. Other venom components have drawn attention as useful scaffolds for the development of drugs. This review summarizes the most promising candidates for drug development that have been isolated from scorpion venoms.


Assuntos
Produtos Biológicos/análise , Descoberta de Drogas/métodos , Venenos de Escorpião/química , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Anti-Infecciosos/isolamento & purificação , Peptídeos Catiônicos Antimicrobianos , Antineoplásicos/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Humanos , Fatores Imunológicos/isolamento & purificação , Bloqueadores dos Canais de Potássio/imunologia , Bloqueadores dos Canais de Potássio/isolamento & purificação
5.
Toxicon ; 76: 23-7, 2013 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-23994427

RESUMO

Potassium channels regulate many neuronal functions, including neuronal excitability and synaptic plasticity, contributing, by these means, to mnemonic processes. In particular, A-type K(+) currents (IA) play a key role in hippocampal synaptic plasticity. Therefore, we evaluated the effect of the peptidic toxin Tx3-1, a selective blocker of IA currents, extracted from the venom of the spider Phoneutria nigriventer, on memory of mice. Administration of Tx3-1 (i.c.v., 300 pmol/site) enhanced both short- and long-term memory consolidation of mice tested in the novel object recognition task. In comparison, 4-aminopyridine (4-AP; i.c.v., 30-300 pmol/site), a non-selective K(+) channel blocker did not alter long-term memory and caused toxic side effects such as circling, freezing and tonic-clonic seizures. Moreover, Tx3-1 (i.c.v., 10-100 pmol/site) restored memory of Aß25-35-injected mice, and exhibited a higher potency to improve memory of Aß25-35-injected mice when compared to control group. These results show the effect of the selective blocker of IA currents Tx3-1 in both short- and long-term memory retention and in memory impairment caused by Aß25-35, reinforcing the role of IA in physiological and pathological memory processes.


Assuntos
Memória/efeitos dos fármacos , Neuropeptídeos/farmacologia , Neurotoxinas/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Venenos de Aranha/química , 4-Aminopiridina/efeitos adversos , 4-Aminopiridina/farmacologia , Animais , Masculino , Camundongos , Neuropeptídeos/isolamento & purificação , Neurotoxinas/isolamento & purificação , Bloqueadores dos Canais de Potássio/isolamento & purificação , Canais de Potássio , Reconhecimento Psicológico , Aranhas/química
6.
Mar Drugs ; 11(6): 2069-112, 2013 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-23771044

RESUMO

The Kunitz-type protease inhibitors are the best-characterized family of serine protease inhibitors, probably due to their abundance in several organisms. These inhibitors consist of a chain of ~60 amino acid residues stabilized by three disulfide bridges, and was first observed in the bovine pancreatic trypsin inhibitor (BPTI)-like protease inhibitors, which strongly inhibit trypsin and chymotrypsin. In this review we present the protease inhibitors (PIs) described to date from marine venomous animals, such as from sea anemone extracts and Conus venom, as well as their counterparts in terrestrial venomous animals, such as snakes, scorpions, spiders, Anurans, and Hymenopterans. More emphasis was given to the Kunitz-type inhibitors, once they are found in all these organisms. Their biological sources, specificity against different proteases, and other molecular blanks (being also K+ channel blockers) are presented, followed by their molecular diversity. Whereas sea anemone, snakes and other venomous animals present mainly Kunitz-type inhibitors, PIs from Anurans present the major variety in structure length and number of Cys residues, with at least six distinguishable classes. A representative alignment of PIs from these venomous animals shows that, despite eventual differences in Cys assignment, the key-residues for the protease inhibitory activity in all of them occupy similar positions in primary sequence. The key-residues for the K+ channel blocking activity was also compared.


Assuntos
Organismos Aquáticos/química , Bloqueadores dos Canais de Potássio/farmacologia , Inibidores de Proteases/farmacologia , Animais , Humanos , Toxinas Marinhas/química , Toxinas Marinhas/isolamento & purificação , Bloqueadores dos Canais de Potássio/isolamento & purificação , Inibidores de Proteases/isolamento & purificação , Peçonhas/química , Peçonhas/isolamento & purificação
7.
Peptides ; 46: 40-6, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23684923

RESUMO

Opisthacanthus cayaporum belongs to the Liochelidae family, and the scorpions from this genus occur in southern Africa, Central America and South America and, therefore, can be considered a true Gondwana heritage. In this communication, the isolation, primary structure characterization, and K⁺-channel blocking activity of new peptide from this scorpion venom are reported. OcyKTx2 is a 34 amino acid long peptide with four disulfide bridges and molecular mass of 3807 Da. Electrophysiological assays conducted with pure OcyKTx2 showed that this toxin reversibly blocks Shaker B K⁺-channels with a Kd of 82 nM, and presents an even better affinity toward hKv1.3, blocking it with a Kd of ∼18 nM. OcyKTx2 shares high sequence identity with peptides belonging to subfamily 6 of α-KTxs that clustered very closely in the phylogenetic tree included here. Sequence comparison, chain length and number of disulfide bridges analysis classify OcyKTx2 into subfamily 6 of the α-KTx scorpion toxins (systematic name, α-KTx6.17).


Assuntos
Canal de Potássio Kv1.3/antagonistas & inibidores , Peptídeos/metabolismo , Venenos de Escorpião/metabolismo , Superfamília Shaker de Canais de Potássio/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Células Cultivadas , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Peptídeos/química , Peptídeos/isolamento & purificação , Bloqueadores dos Canais de Potássio/química , Bloqueadores dos Canais de Potássio/isolamento & purificação , Bloqueadores dos Canais de Potássio/metabolismo , Ligação Proteica , Venenos de Escorpião/química , Venenos de Escorpião/isolamento & purificação , Escorpiões/metabolismo , Alinhamento de Sequência , Análise de Sequência de Proteína
8.
Mar Drugs ; 11(3): 655-79, 2013 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-23466933

RESUMO

Sea anemone (Cnidaria, Anthozoa) venom is an important source of bioactive compounds used as tools to study the pharmacology and structure-function of voltage-gated K+ channels (KV). These neurotoxins can be divided into four different types, according to their structure and mode of action. In this work, for the first time, two toxins were purified from the venom of Bunodosoma caissarum population from Saint Peter and Saint Paul Archipelago, Brazil. Sequence alignment and phylogenetic analysis reveals that BcsTx1 and BcsTx2 are the newest members of the sea anemone type 1 potassium channel toxins. Their functional characterization was performed by means of a wide electrophysiological screening on 12 different subtypes of KV channels (KV1.1-KV1.6; KV2.1; KV3.1; KV4.2; KV4.3; hERG and Shaker IR). BcsTx1 shows a high affinity for rKv1.2 over rKv1.6, hKv1.3, Shaker IR and rKv1.1, while Bcstx2 potently blocked rKv1.6 over hKv1.3, rKv1.1, Shaker IR and rKv1.2. Furthermore, we also report for the first time a venom composition and biological activity comparison between two geographically distant populations of sea anemones.


Assuntos
Venenos de Cnidários/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/antagonistas & inibidores , Anêmonas-do-Mar/química , Animais , Brasil , Venenos de Cnidários/química , Fenômenos Eletrofisiológicos , Humanos , Filogenia , Bloqueadores dos Canais de Potássio/química , Bloqueadores dos Canais de Potássio/isolamento & purificação , Ratos , Alinhamento de Sequência
9.
Toxicon ; 58(1): 54-61, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21600910

RESUMO

Voltage-gated potassium channel toxins (KTxs) are basic short chain peptides comprising 23-43 amino acid residues that can be cross-linked by 3 or 4 disulfide bridges. KTxs are classified into four large families: α-, ß-, γ- and κ-KTx. These peptides display varying selectivity and affinity for K(v) channel subtypes. In this work, a novel toxin from the Tityus serrulatus venom was isolated, characterized and submitted to a wide electrophysiological screening on 5 different subtypes of Na(V) channels (Na(V)1.4; Na(V)1.5; Na(V)1.6; Na(V)1.8 and DmNa(V)1) and 12 different subtypes of K(V) channels (K(V)1.1 - K(V)1.6; K(V)2.1; K(V)3.1; K(V)4.2; K(V)4.3; Shaker IR and ERG). This novel peptide, named Ts15, has 36 amino acids, is cross-linked by 3 disulfide bridges, has a molecular mass of 3956 Da and pI around 9. Electrophysiological experiments using patch clamp and the two-electrode voltage clamp techniques show that Ts15 preferentially blocks K(V)1.2 and K(V)1.3 channels with an IC50 value of 196 ± 25 and 508 ± 67 nM, respectively. No effect on Na(V) channels was observed, at all tested concentrations. Since Ts15 shows low amino acid identity with other known KTxs, it was considered a bona fide novel type of scorpion toxin. Ts15 is the unique member of the new α-Ktx21 subfamily and therefore was classified as α-Ktx21.1.


Assuntos
Bloqueadores dos Canais de Potássio/química , Canais de Potássio/química , Venenos de Escorpião/química , Sequência de Aminoácidos , Animais , Dados de Sequência Molecular , Técnicas de Patch-Clamp , Bloqueadores dos Canais de Potássio/isolamento & purificação , Venenos de Escorpião/isolamento & purificação , Escorpiões , Análise de Sequência de Proteína
10.
Biochem Pharmacol ; 76(9): 1142-54, 2008 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-18786511

RESUMO

A novel potassium channel blocker peptide was purified from the venom of the scorpion Centruroides suffusus suffusus by high-performance liquid chromatography and its amino acid sequence was completed by Edman degradation and mass spectrometry analysis. It contains 38 amino acid residues with a molecular weight of 4000.3Da, tightly folded by three disulfide bridges. This peptide, named Css20, was shown to block preferentially the currents of the voltage-dependent K+-channels Kv1.2 and Kv1.3. It did not affect several other ion channels tested at 10 nM concentration. Concentration-response curves of Css20 yielded an IC50 of 1.3 and 7.2 nM for Kv1.2- and Kv1.3-channels, respectively. Interestingly, despite the similar affinities for the two channels the association and dissociation rates of the toxin were much slower for Kv1.2, implying that different interactions may be involved in binding to the two channel types; an implication further supported by in silico docking analyses. Based on the primary structure of Css20, the systematic nomenclature proposed for this toxin is alpha-KTx 2.13.


Assuntos
Canal de Potássio Kv1.2/antagonistas & inibidores , Canal de Potássio Kv1.3/antagonistas & inibidores , Bloqueadores dos Canais de Potássio/farmacologia , Venenos de Escorpião/farmacologia , Sequência de Aminoácidos , Animais , Células COS , Linhagem Celular Tumoral , Células Cultivadas , Chlorocebus aethiops , Humanos , Canal de Potássio Kv1.2/fisiologia , Canal de Potássio Kv1.3/fisiologia , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Bloqueadores dos Canais de Potássio/isolamento & purificação , Ratos , Venenos de Escorpião/química , Venenos de Escorpião/isolamento & purificação , Escorpiões
11.
Neurochem Res ; 33(8): 1525-33, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18338253

RESUMO

Voltage-gated potassium channels of the ether-a-go-go related gene (ERG) family are implicated in many important cellular processes. Three such genes have been cloned (erg1, erg2 and erg3) and shown to be expressed in the central nervous system (CNS) of mammalians. This communication describes the isolation and characterization of two isoforms of scorpion toxin (CeErg4 and CeErg5, systematic nomenclature gamma-KTx1.7 and gamma-KTx1.8, respectively) that can discriminate the various subtypes of ERG channels of human and rat. These peptides were purified from the venom of the Mexican scorpion Centruroides elegans elegans. They contain 42 amino acid residues, tightly folded by four disulfide bridges. Both peptides block in a reversible manner human and rat ERG1 channels, but have no effect on human ERG2. They also block completely and irreversibly the rat ERG2 and the human ERG3 channels hence are excellent tools for the discrimination of the various sub-types of ion-channels studied.


Assuntos
Canais de Potássio Éter-A-Go-Go/metabolismo , Peptídeos/isolamento & purificação , Peptídeos/metabolismo , Bloqueadores dos Canais de Potássio , Venenos de Escorpião/isolamento & purificação , Venenos de Escorpião/metabolismo , Escorpiões/química , Sequência de Aminoácidos , Animais , Células CHO , Cricetinae , Cricetulus , Canais de Potássio Éter-A-Go-Go/genética , Humanos , Dados de Sequência Molecular , Técnicas de Patch-Clamp , Peptídeos/genética , Bloqueadores dos Canais de Potássio/isolamento & purificação , Bloqueadores dos Canais de Potássio/metabolismo , Ratos , Venenos de Escorpião/genética , Alinhamento de Sequência
12.
Cell Mol Life Sci ; 65(1): 187-200, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18030427

RESUMO

Among the scorpion venom components whose function are poorly known or even show contrasting pharmacological results are those called "orphan peptides". The most widely distributed are named beta-KTx or scorpine-like peptides. They contain three disulfide bridges with two recognizable domains: a freely moving N-terminal amino acid sequence and a tightly folded C-terminal region with a cysteine-stabilized alpha/beta (CS-alphabeta) motif. Four such peptides and three cloned genes are reported here. They were assayed for their cytolytic, antimicrobial and K (+) channel-blocking activities. Two main characteristics were found: the existence of an unusual structural and functional diversity, whereby the full-length peptide can lyse cells or kill microorganisms, and a C-terminal domain containing the CS-alphabeta motif that can block K (+) channels. Furthermore, sequence analyses and phylogenetic reconstructions are used to discuss the evolution of this type of peptide and to highlight the versatility of the CS-alphabeta structures.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Defensinas/química , Peptídeos/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Venenos de Escorpião/química , Venenos de Escorpião/farmacologia , Animais , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Defensinas/isolamento & purificação , Evolução Molecular , Neurotoxinas , Peptídeos/isolamento & purificação , Bloqueadores dos Canais de Potássio/isolamento & purificação
13.
Toxicon ; 48(8): 1046-53, 2006 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-17030052

RESUMO

A novel toxin was identified, purified and characterized from the venom of the Mexican scorpion Hadrurus gertschi (abbreviated HgeTx1). It has a molecular mass of 3950 atomic mass units (a.m.u.) and contains 36 amino acids with four disulfide bridges established between Cys1-Cys5, Cys2-Cys6, Cys3-Cys7 and Cys4-Cys8. It blocks reversibly the Shaker B K(+)-channels with a Kd of 52nM. HgeTx1 shares 60%, 45% and 40% sequence identity, respectively, with Heterometrus spinnifer toxin1 (HsTX1), Scorpio maurus K(+)-toxin (maurotoxin) and Pandinus imperator toxin1 (Pi1), all four-disulfide bridged toxins. It is 57-58% identical with the other scorpion K(+)-channel toxins that contain only three disulfide bridges. Sequence comparison, chain length and number of disulfide bridges analysis classify HgeTx1 into subfamily 6 of the alpha-KTx scorpion toxins (systematic name: alpha-KTx 6.14).


Assuntos
Bloqueadores dos Canais de Potássio/química , Venenos de Escorpião/química , Superfamília Shaker de Canais de Potássio/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Células Cultivadas , Insetos/citologia , Dados de Sequência Molecular , Bloqueadores dos Canais de Potássio/isolamento & purificação , Venenos de Escorpião/isolamento & purificação , Escorpiões/química , Alinhamento de Sequência
14.
Biochim Biophys Acta ; 1764(1): 76-84, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16309982

RESUMO

The Colombian scorpion Tityus pachyurus is toxic to humans and is capable of producing fatal accidents, but nothing is known about its venom components. This communication reports the separation of at least 57 fractions from the venom by high performance liquid chromatography. From these, at least 104 distinct molecular weight compounds were identified by mass spectrometry analysis. The complete amino acid sequences of three peptides were determined and the partial sequences of three others were also identified. Electrophysiological experiments conducted with ion-channels expressed heterologously on Sf9 cells showed the presence of a potent Shaker B K(+)-channel blocker. This peptide (trivial name Tpa1) contains 23 amino acid residues closely packed by three disulfide bridges with a molecular mass of 2,457 atomic mass units. It is the third member of the sub-family 13, for which the systematic name is proposed to be alpha-KTx13.3. The mice assay showed clearly the presence of toxic peptides to mammals. One of them named Tpa2, containing 65 amino acid residues with molecular mass of 7,522.5 atomic mass units, is stabilized by four disulfide bridges. It was shown to modify the Na(+)-currents of F-11 and TE671 cells in culture, similar to the beta scorpion toxins. These results demonstrate the presence of toxic peptides in the venom of T. pachyurus and confirm that accidents with this species of scorpion should be considered an important human hazard in Colombia.


Assuntos
Canais de Potássio/efeitos dos fármacos , Venenos de Escorpião/química , Venenos de Escorpião/toxicidade , Canais de Sódio/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Humanos , Técnicas In Vitro , Dose Letal Mediana , Camundongos , Dados de Sequência Molecular , Bloqueadores dos Canais de Potássio/química , Bloqueadores dos Canais de Potássio/isolamento & purificação , Bloqueadores dos Canais de Potássio/toxicidade , Proteômica , Venenos de Escorpião/genética , Escorpiões/química , Escorpiões/genética , Escorpiões/patogenicidade , Homologia de Sequência de Aminoácidos , Superfamília Shaker de Canais de Potássio/antagonistas & inibidores , Bloqueadores dos Canais de Sódio/química , Bloqueadores dos Canais de Sódio/isolamento & purificação , Bloqueadores dos Canais de Sódio/toxicidade , Espectrometria de Massas por Ionização por Electrospray
15.
Biochim Biophys Acta ; 1601(2): 123-31, 2002 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-12445473

RESUMO

Two novel toxic peptides (Tc30 and Tc32) were isolated and characterized from the venom of the Brazilian scorpion Tityus cambridgei. The first have 37 and the second 35 amino acid residues, with molecular masses of 3,871.8 and 3,521.5, respectively. Both contain three disulfide bridges but share only 27% identity. They are relatively potent inhibitors of K(+)-currents in human T lymphocytes with K(d) values of 10 nM for Tc32 and 16 nM for Tc30, but they are less potent or quite poor blockers of Shaker B K(+)-channels, with respective K(d) values of 74 nM and 4.7 microM. Tc30 has a lysine in position 27 and a tyrosine at position 36 identical to those of charybdotoxin. These two positions conform the dyad considered essential for activity. On the contrary, Tc32 has a serine in the position equivalent to lysine 27 of charybdotoxin and does not contain any aromatic amino acid. Due to its unique primary sequence and to its distinctive preference for K(+)-channels of T lymphocytes, it was classified as the first example of a new subfamily of K(+)-channel-specific peptides (alpha-KT x 18.1). Tc30 is a member of the Tityus toxin II-9 subfamily and was given the number alpha-KT x 4.4.


Assuntos
Peptídeos/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/toxicidade , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio/efeitos dos fármacos , Venenos de Escorpião/toxicidade , Sequência de Aminoácidos , Animais , Brasil , Humanos , Canal de Potássio Kv1.3 , Dados de Sequência Molecular , Peptídeos/genética , Bloqueadores dos Canais de Potássio/química , Bloqueadores dos Canais de Potássio/isolamento & purificação , Canais de Potássio/genética , Venenos de Escorpião/química , Venenos de Escorpião/isolamento & purificação , Escorpiões , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Superfamília Shaker de Canais de Potássio , Spodoptera , Transfecção
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