| 词条 | Discrepin |
| 释义 |
Discrepin (α-KTx15.6) is a peptide from the venom of the Venezuelan scorpion Tityus discrepans.[1] It acts as a neurotoxin by irreversibly blocking A-type voltage-dependent K+-channels. Etymology and sourceDiscrepin is named after its source: a Venezuelan scorpion called Tityus discrepans.[1] Its systematic number is α-KTx15.6.[2] ChemistryThe subfamily α-KTx15 consists of 6 toxins. The first five toxins of this subfamily are very much alike, but discrepin only shares 50% amino acid homology with other members of this subfamily.[1] Discrepin contains 38 amino acid residues. It has a polyglutamic acid at its N-terminal region.[3] Discrepin has the α and β folds that are characteristic of scorpion toxins.[2] It consists of one α-helix and three β-sheet helix strands. The α-helix is formed from amino acid Ser11 until Arg21. The three antiparallel β-sheets are formed from amino acid Ile2 until Lys7, Ala27 until Cys29 and Arg33 until Cys36. TargetDiscrepin blocks voltage-gated Shal-type (Kv4.x) K+ channels in cerebellar granular cells.[1][2] These A-type K+ channels regulate firing frequency, spike initiation and the waveform of action potentials.[2] Discrepin has yet only been tested in cerebellar cells, however, Kv4.x family channels are in general highly expressed in the brain, heart and smooth muscles.[4] Competition experiments showed that discrepin inhibits the binding of scorpion toxin BmTx3 to its receptor site, where other K+ channel blockers (Kv1-, Kv3.4-, Kv4.2/4.3 family blockers) were unable to compete with this toxin. These results support the hypothesis that discrepin can bind to a very specific and unique type of Kv4.x receptor channels.[2] The residues of discrepin that are important for blocking these channels have not yet been clarified. However, it is clear that the N-terminal plays a role in the binding affinity.[3] The stoichiometry of toxin binding to the potassium channel is 1:1.[3] Mode of actionDiscrepin specifically blocks the IA currents (fast transient, low-voltage-activated currents) of voltage-dependent K+ channels. Inhibition of these K+ currents occurs in an irreversible manner, i.e. washing out of the toxin gives no recovery of the currents.[1][2] The kinetics of the channel are not affected by discrepin and the blockage is independent of the holding potential.[2] ToxicityThe half-effective dose (IC50) is 190 ± 30 nM.[1] References1. ^1 2 3 4 5 {{cite journal |vauthors=D'Suze G, Batista CV, Frau A |title=Discrepin, a new peptide of the sub-family alpha-ktx15, isolated from the scorpion Tityus discrepans irreversibly blocks K+ -channels (IA currents) of cerebellum granular cells |journal=Archives of Biochemistry and Biophysics |volume=430 |issue=2 |pages=256–63 |date=October 2004 |pmid=15369825 |doi=10.1016/j.abb.2004.07.010|display-authors=etal}} 2. ^1 2 3 4 5 6 {{cite journal |vauthors=Prochnicka-Chalufour A, Corzo G, Satake H |title=Solution structure of discrepin, a new K+-channel blocking peptide from the alpha-KTx15 subfamily |journal=Biochemistry |volume=45 |issue=6 |pages=1795–804 |date=February 2006 |pmid=16460026 |doi=10.1021/bi0519248|display-authors=etal}} 3. ^1 2 {{cite journal |vauthors=Romeo S, Corzo G, Vasile A, Satake H, Prestipino G, Possani LD |title=A positive charge at the N-terminal segment of Discrepin increases the blocking effect of K+ channels responsible for the IA currents in cerebellum granular cells |journal=Biochimica et Biophysica Acta |volume=1780 |issue=4 |pages=750–5 |date=April 2008 |pmid=18280256 |doi=10.1016/j.bbagen.2008.01.012}} 4. ^{{cite journal |vauthors=Birnbaum SG, Varga AW, Yuan LL, Anderson AE, Sweatt JD, Schrader LA |title=Structure and function of Kv4-family transient potassium channels |journal=Physiological Reviews |volume=84 |issue=3 |pages=803–33 |date=July 2004 |pmid=15269337 |doi=10.1152/physrev.00039.2003}} 2 : Ion channel toxins|Neurotoxins |
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