2i1t: Difference between revisions

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[[Image:2i1t.gif|left|200px]]<br /><applet load="2i1t" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:2i1t.gif|left|200px]]<br /><applet load="2i1t" size="350" color="white" frame="true" align="right" spinBox="true"

caption="2i1t" />

'''Solution structure of Jingzhaotoxin-III, a novel toxin inhibiting both Nav and Kv channels'''<br />

==Overview==

We have isolated a cardiotoxin, denoted jingzhaotoxin-III (JZTX-III), from, the venom of the Chinese spider Chilobrachys jingzhao. The toxin contains, 36 residues stabilized by three intracellular disulfide bridges (I-IV, II-V, and III-VI), assigned by a chemical strategy of partial reduction, and sequence analysis. Cloned and sequenced using 3'-rapid amplification, of cDNA ends and 5'-rapid amplification of cDNA ends, the full-length cDNA, encoded a 63-residue precursor of JZTX-III. Different from other spider, peptides, it contains an uncommon endoproteolytic site (-X-Ser-) anterior, to mature protein and the intervening regions of 5 residues, which is the, smallest in spider toxin cDNAs identified to date. Under whole cell, recording, JZTX-III showed no effects on voltage-gated sodium channels, (VGSCs) or calcium channels in dorsal root ganglion neurons, whereas it, significantly inhibited tetrodotoxin-resistant VGSCs with an IC(50) value, of 0.38 microm in rat cardiac myocytes. Different from scorpion, beta-toxins, it caused a 10-mV depolarizing shift in the channel, activation threshold. The binding site for JZTX-III on VGSCs is further, suggested to be site 4 with a simple competitive assay, which at 10 microm, eliminated the slowing currents induced by Buthus martensi Karsch I, (BMK-I, scorpion alpha-like toxin) completely. JZTX-III shows higher, selectivity for VGSC isoforms than other spider toxins affecting VGSCs, and the toxin hopefully represents an important ligand for discriminating, cardiac VGSC subtype.

We have isolated a cardiotoxin, denoted jingzhaotoxin-III (JZTX-III), from the venom of the Chinese spider Chilobrachys jingzhao. The toxin contains 36 residues stabilized by three intracellular disulfide bridges (I-IV, II-V, and III-VI), assigned by a chemical strategy of partial reduction and sequence analysis. Cloned and sequenced using 3'-rapid amplification of cDNA ends and 5'-rapid amplification of cDNA ends, the full-length cDNA encoded a 63-residue precursor of JZTX-III. Different from other spider peptides, it contains an uncommon endoproteolytic site (-X-Ser-) anterior to mature protein and the intervening regions of 5 residues, which is the smallest in spider toxin cDNAs identified to date. Under whole cell recording, JZTX-III showed no effects on voltage-gated sodium channels (VGSCs) or calcium channels in dorsal root ganglion neurons, whereas it significantly inhibited tetrodotoxin-resistant VGSCs with an IC(50) value of 0.38 microm in rat cardiac myocytes. Different from scorpion beta-toxins, it caused a 10-mV depolarizing shift in the channel activation threshold. The binding site for JZTX-III on VGSCs is further suggested to be site 4 with a simple competitive assay, which at 10 microm eliminated the slowing currents induced by Buthus martensi Karsch I (BMK-I, scorpion alpha-like toxin) completely. JZTX-III shows higher selectivity for VGSC isoforms than other spider toxins affecting VGSCs, and the toxin hopefully represents an important ligand for discriminating cardiac VGSC subtype.

==About this Structure==

2I1T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Chilobrachys_jingzhao Chilobrachys jingzhao]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=2I1T OCA].

2I1T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Chilobrachys_jingzhao Chilobrachys jingzhao]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I1T OCA].

==Reference==

Line 18:

[[Category: cardiac myocytes]]

[[Category: jingzhaotoxin-iii]]

[[Category: kv2.1 channel]]

[[Category: kv2 1 channel]]

[[Category: nav channel]]

[[Category: solution structure]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 12:06:~~17 2007~~''

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@@ Line 1: / Line 1: @@
-[[Image:2i1t.gif|left|200px]]<br /><applet load="2i1t" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2i1t.gif|left|200px]]<br /><applet load="2i1t" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2i1t" />
 '''Solution structure of Jingzhaotoxin-III, a novel toxin inhibiting both Nav and Kv channels'''<br />
 ==Overview==
-We have isolated a cardiotoxin, denoted jingzhaotoxin-III (JZTX-III), from, the venom of the Chinese spider Chilobrachys jingzhao. The toxin contains, 36 residues stabilized by three intracellular disulfide bridges (I-IV, II-V, and III-VI), assigned by a chemical strategy of partial reduction, and sequence analysis. Cloned and sequenced using 3'-rapid amplification, of cDNA ends and 5'-rapid amplification of cDNA ends, the full-length cDNA, encoded a 63-residue precursor of JZTX-III. Different from other spider, peptides, it contains an uncommon endoproteolytic site (-X-Ser-) anterior, to mature protein and the intervening regions of 5 residues, which is the, smallest in spider toxin cDNAs identified to date. Under whole cell, recording, JZTX-III showed no effects on voltage-gated sodium channels, (VGSCs) or calcium channels in dorsal root ganglion neurons, whereas it, significantly inhibited tetrodotoxin-resistant VGSCs with an IC(50) value, of 0.38 microm in rat cardiac myocytes. Different from scorpion, beta-toxins, it caused a 10-mV depolarizing shift in the channel, activation threshold. The binding site for JZTX-III on VGSCs is further, suggested to be site 4 with a simple competitive assay, which at 10 microm, eliminated the slowing currents induced by Buthus martensi Karsch I, (BMK-I, scorpion alpha-like toxin) completely. JZTX-III shows higher, selectivity for VGSC isoforms than other spider toxins affecting VGSCs, and the toxin hopefully represents an important ligand for discriminating, cardiac VGSC subtype.
+We have isolated a cardiotoxin, denoted jingzhaotoxin-III (JZTX-III), from the venom of the Chinese spider Chilobrachys jingzhao. The toxin contains 36 residues stabilized by three intracellular disulfide bridges (I-IV, II-V, and III-VI), assigned by a chemical strategy of partial reduction and sequence analysis. Cloned and sequenced using 3'-rapid amplification of cDNA ends and 5'-rapid amplification of cDNA ends, the full-length cDNA encoded a 63-residue precursor of JZTX-III. Different from other spider peptides, it contains an uncommon endoproteolytic site (-X-Ser-) anterior to mature protein and the intervening regions of 5 residues, which is the smallest in spider toxin cDNAs identified to date. Under whole cell recording, JZTX-III showed no effects on voltage-gated sodium channels (VGSCs) or calcium channels in dorsal root ganglion neurons, whereas it significantly inhibited tetrodotoxin-resistant VGSCs with an IC(50) value of 0.38 microm in rat cardiac myocytes. Different from scorpion beta-toxins, it caused a 10-mV depolarizing shift in the channel activation threshold. The binding site for JZTX-III on VGSCs is further suggested to be site 4 with a simple competitive assay, which at 10 microm eliminated the slowing currents induced by Buthus martensi Karsch I (BMK-I, scorpion alpha-like toxin) completely. JZTX-III shows higher selectivity for VGSC isoforms than other spider toxins affecting VGSCs, and the toxin hopefully represents an important ligand for discriminating cardiac VGSC subtype.
 ==About this Structure==
-I1T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Chilobrachys_jingzhao Chilobrachys jingzhao]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2I1T OCA].
+I1T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Chilobrachys_jingzhao Chilobrachys jingzhao]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I1T OCA].
 ==Reference==
@@ Line 18: / Line 18: @@
 [[Category: cardiac myocytes]]
 [[Category: jingzhaotoxin-iii]]
-[[Category: kv2.1 channel]]
+[[Category: kv2 1 channel]]
 [[Category: nav channel]]
 [[Category: solution structure]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 12:06:17 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:48:16 2008''