6ggz

From Proteopedia

NMR structure of the scorpion toxin AmmTx3

Structural highlights

6ggz is a 1 chain structure with sequence from Androctonus mauritanicus mauritanicus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 10 models
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KA153_ANDMA Blocker of A-type voltage-gated potassium channels of striated neurons (PubMed:12473099). Has been shown to block ERG1/Kv11.1/KCNH2 potassium channels (IC(50)=7.9 uM) (PubMed:18687312). In adult rat brain, it binds to sites in the striatum, and cerebellum. It shares the same target in rat brain than AaTX1 (AC Q867F4) and BmTX3 (AC Q8I0L5).^[1] ^[2]

Publication Abstract from PubMed

The scorpion toxin AmmTx3 is a specific blocker of Kv4 channels. It was shown to have interesting potential for neurological disorders. In this study, we report the first chemical synthesis of AmmTx3 by using the native chemical ligation strategy and validate its biological activity. We determined its 3D structure by nuclear magnetic resonance spectroscopy, and pointed out that AmmTx3 possesses the well-known CSalphabeta structural motif, which is found in a large number of scorpion toxins. Overall, this study establishes an easy synthetic access to biologically active AmmTx3 toxin.

Synthesis by native chemical ligation and characterization of the scorpion toxin AmmTx3.,Zoukimian C, Meudal H, De Waard S, Ouares KA, Nicolas S, Canepari M, Beroud R, Landon C, De Waard M, Boturyn D Bioorg Med Chem. 2019 Jan 1;27(1):247-253. doi: 10.1016/j.bmc.2018.12.009. Epub, 2018 Dec 6. PMID:30529150^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Vacher H, Alami M, Crest M, Possani LD, Bougis PE, Martin-Eauclaire MF. Expanding the scorpion toxin alpha-KTX 15 family with AmmTX3 from Androctonus mauretanicus. Eur J Biochem. 2002 Dec;269(24):6037-41. PMID:12473099
↑ Abdel-Mottaleb Y, Corzo G, Martin-Eauclaire MF, Satake H, Ceard B, Peigneur S, Nambaru P, Bougis PE, Possani LD, Tytgat J. A common "hot spot" confers hERG blockade activity to alpha-scorpion toxins affecting K+ channels. Biochem Pharmacol. 2008 Sep 15;76(6):805-15. doi: 10.1016/j.bcp.2008.07.008. Epub, 2008 Jul 18. PMID:18687312 doi:http://dx.doi.org/10.1016/j.bcp.2008.07.008
↑ Zoukimian C, Meudal H, De Waard S, Ouares KA, Nicolas S, Canepari M, Beroud R, Landon C, De Waard M, Boturyn D. Synthesis by native chemical ligation and characterization of the scorpion toxin AmmTx3. Bioorg Med Chem. 2019 Jan 1;27(1):247-253. doi: 10.1016/j.bmc.2018.12.009. Epub, 2018 Dec 6. PMID:30529150 doi:http://dx.doi.org/10.1016/j.bmc.2018.12.009