Tst26, a novel peptide blocker of Kv1.2 and Kv1.3 channels from the venom of Tityus stigmurus.
ABSTRACT Using high-performance liquid chromatography Tst26, a novel potassium channel blocker peptide, was purified from the venom of the Brazilian scorpion Tityus stigmurus. Its primary structure was determined by means of automatic Edman degradation and mass spectrometry analysis. The peptide is composed of 37 amino acid residues and tightly folded through three disulfide bridges, similar to other K(+) channel blocking peptides purified from scorpion venoms. It contains the "essential dyad" for K(+) channel recognition comprised of a lysine at position 27 and a tyrosine at position 36. Electrophysiological assays revealed that Tst26 blocked hKv1.2 and hKv1.3 channels with high affinity (K(d)=1.9 nM and 10.7 nM, respectively) while it did not affect several other ion channels (mKv1.1, hKv1.4, hKv1.5, hERG, hIKCa1, hBK, hNav1.5) tested at 10 nM concentration. The voltage-dependent steady-state parameters of K(+) channel gating were unaffected by the toxin in both channels, but due to the fast association and dissociation kinetics Tst26 slowed the rate of inactivation of Kv1.3 channels. Based on the primary structure, the systematic nomenclature proposed for this peptide is alpha-KTx 4.6.
- Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 12/2011; 70(9):2099-105. · 1.58 Impact Factor
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ABSTRACT: Potassium channels are involved in the maintenance of resting membrane potential, control of cardiac and neuronal excitability, neurotransmitters release, muscle contractility and hormone secretion. The Tityus stigmurus scorpion is widely distributed in Northeastern Brazil and known to cause severe human envenomations, inducing pain, hypoesthesia, edema, erythema, paresthesia, headaches and vomiting. Most potassium channel blocking peptides that have been purified from scorpion venoms contain 30-40 amino acids with three or four disulfide bridges. These peptides belong to α-KTx subfamily. On the other hand, the β-KTx subfamily is poorly characterized, though it is very representative in some scorpion venoms. A transcriptomic approach of Tityus stigmurus scorpions developed by our group revealed the repertoire of possible molecules present in the venom, including many toxins of the β-KTx subfamily. One of the ESTs found, named TSTI0003C has a cDNA sequence of 538 bp codifying a mature protein with 47 amino acid residues, corresponding to 5,299 Da. This β-KTx peptide is a new member of the BmTXKβ-related toxins, and was here named TstKMK. The three-dimensional structure of this potassium channel toxin of the T. stigmurus scorpion was obtained by computational modeling and refined by molecular dynamic simulations. Furthermore, we have made docking simulations using a Shaker Kv-1.2 potassium channel from rats as receptor model and proposed which amino acid residues and interactions could be involved in its blockade.Biochemical and Biophysical Research Communications 11/2012; · 2.28 Impact Factor
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ABSTRACT: Peptide toxins synthesized by venomous animals have been extensively studied in the last decades. To be useful to the scientific community, this knowledge has been stored, annotated and made easy to retrieve by several databases. The aim of this article is to present what type of information users can access from each database. ArachnoServer and ConoServer focus on spider toxins and cone snail toxins, respectively. UniProtKB, a generalist protein knowledgebase, has an animal toxin-dedicated annotation program that includes toxins from all venomous animals. Finally, the ATDB metadatabase compiles data and annotations from other databases and provides toxin ontology.Toxins 02/2010; 2(2):262-82. · 2.48 Impact Factor