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[Effects of Arg20 mutation on sodium channels activity of JZTX-V].
Sheng Wu Gong Cheng Xue Bao. 2008 Jul; 24(7):1228-32.SW

Abstract

Jingzhaotoxin-V(JZTX-V) isolated from the venom of the spider Chilobrachys jingzhao is a novel potent inhibitor that acts on tetrodotoxin-resistant and tetrodotoxin-sensitive sodium channels in adult rat dorsal root ganglion(DRG) neurons. It is a 29-residue polypeptide toxin including three disulfide bridges. To investigate the structure-function relationship of the toxin, a mutant of JZTX-V in which Arg20 was substituted by Ala, was synthesized by solid-phase chemistry method with Fmoc-protected amino acids on the PS3 automated peptide synthesizer. The synthetic linear peptide was then purified by reversed-phase high performance liquid chromatography and oxidatively refolded under the optimal conditions. The refolded product was analyzed by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry(MALDI-TOF MS) and electrophysiological experiments for its relative molecular weight and prohibitive activity of sodium channels respectively. The present findings show that the prohibitive effect of R20A-JZTX-V on TTX-S sodium channels in DRG neurons is almost the same as that of native JZTX-V, suggesting that Arg20 does not play any important role in inhibiting TTX-S sodium currents in DRG neurons. In contrast, the prohibitive level of R20A-JZTX-V on TTX-R sodium channels is reduced by at last 18.3 times, indicating that Arg20 is a key amino acid residue relative to the bioactivity of JZTX-V. It is presumed that the decrease in activity of R20A-JZTX-V is due to the changes of the property in the binding site in TTX-R sodium channels.

Authors+Show Affiliations

The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha 410081, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

18837400

Citation

Zeng, Xiongzhi, et al. "[Effects of Arg20 Mutation On Sodium Channels Activity of JZTX-V]." Sheng Wu Gong Cheng Xue Bao = Chinese Journal of Biotechnology, vol. 24, no. 7, 2008, pp. 1228-32.
Zeng X, Deng M, Pi J, et al. [Effects of Arg20 mutation on sodium channels activity of JZTX-V]. Sheng Wu Gong Cheng Xue Bao. 2008;24(7):1228-32.
Zeng, X., Deng, M., Pi, J., Quan, M., Wang, X., & Liang, S. (2008). [Effects of Arg20 mutation on sodium channels activity of JZTX-V]. Sheng Wu Gong Cheng Xue Bao = Chinese Journal of Biotechnology, 24(7), 1228-32.
Zeng X, et al. [Effects of Arg20 Mutation On Sodium Channels Activity of JZTX-V]. Sheng Wu Gong Cheng Xue Bao. 2008;24(7):1228-32. PubMed PMID: 18837400.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Effects of Arg20 mutation on sodium channels activity of JZTX-V]. AU - Zeng,Xiongzhi, AU - Deng,Meichun, AU - Pi,Jianhui, AU - Quan,Miaohua, AU - Wang,Xianchun, AU - Liang,Songping, PY - 2008/10/8/pubmed PY - 2009/9/9/medline PY - 2008/10/8/entrez SP - 1228 EP - 32 JF - Sheng wu gong cheng xue bao = Chinese journal of biotechnology JO - Sheng Wu Gong Cheng Xue Bao VL - 24 IS - 7 N2 - Jingzhaotoxin-V(JZTX-V) isolated from the venom of the spider Chilobrachys jingzhao is a novel potent inhibitor that acts on tetrodotoxin-resistant and tetrodotoxin-sensitive sodium channels in adult rat dorsal root ganglion(DRG) neurons. It is a 29-residue polypeptide toxin including three disulfide bridges. To investigate the structure-function relationship of the toxin, a mutant of JZTX-V in which Arg20 was substituted by Ala, was synthesized by solid-phase chemistry method with Fmoc-protected amino acids on the PS3 automated peptide synthesizer. The synthetic linear peptide was then purified by reversed-phase high performance liquid chromatography and oxidatively refolded under the optimal conditions. The refolded product was analyzed by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry(MALDI-TOF MS) and electrophysiological experiments for its relative molecular weight and prohibitive activity of sodium channels respectively. The present findings show that the prohibitive effect of R20A-JZTX-V on TTX-S sodium channels in DRG neurons is almost the same as that of native JZTX-V, suggesting that Arg20 does not play any important role in inhibiting TTX-S sodium currents in DRG neurons. In contrast, the prohibitive level of R20A-JZTX-V on TTX-R sodium channels is reduced by at last 18.3 times, indicating that Arg20 is a key amino acid residue relative to the bioactivity of JZTX-V. It is presumed that the decrease in activity of R20A-JZTX-V is due to the changes of the property in the binding site in TTX-R sodium channels. SN - 1000-3061 UR - https://www.unboundmedicine.com/medline/citation/18837400/[Effects_of_Arg20_mutation_on_sodium_channels_activity_of_JZTX_V]_ L2 - https://www.lens.org/lens/search?q=citation_id:18837400 DB - PRIME DP - Unbound Medicine ER -