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Peptide record

TPDB72189

Neurotoxin standard
62 amino acids
Basic Information
3D PDB MODEL
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TPDB72189
Neurotoxin
Toxicity and safety peptides
NTxPred2
standard
No
A 62-aa standard natural neurotoxin peptide sequence curated from NTxPred2, with an available 3D structural model.
Sequence
MKVLILIMIIASLMIMGVEMDRDSCVDKSRCAKYGYYQECQDCCKNAGHNGGTCMFFKCKCA
Physicochemical Analysis
C295H478N80O86S14
PW
C
6970.36
7.84
9
6
26
+2
7.98
0.179
70.81
Mammalian: 30 hour Yeast: >20 hour E.coli: >10 hour
4970
71.30
19
Residue Composition
number
4
A
2
R
2
N
4
D
8
C
2
E
2
Q
5
G
1
H
5
I
3
L
6
K
6
M
2
F
0
P
3
S
1
T
0
W
3
Y
3
V
Amino Acid Distribution
A: 4 R: 2 N: 2 D: 4 C: 8 E: 2 Q: 2 G: 5 H: 1 I: 5 L: 3 K: 6 M: 6 F: 2 P: 0 S: 3 T: 1 W: 0 Y: 3 V: 3
Chemical Descriptors
62
C295H478N80O86S14
6970.36
7.84
+2
7.98
0.179
Evidence Records 1 records
Evidence 1 Activity

Activity

Neurotoxin
FUNCTION: Blocks human and rat Kv11.1/KCNH2/ERG1 and Kv11.3/KCNH7/ERG3, as well as rat (but not human) Kv11.2/KCNH6/ERG2 (PubMed:11755529, PubMed:11864985, PubMed:16497878, PubMed:17369411, PubMed:20600425) by binding to channel outer vestibule (S5P domain) with a 1:1 stoichiometry (PubMed:11755529, PubMed:11864985, PubMed:17369411, PubMed:20600425). Inhibition data are the following: hERG1 (reversible, IC(50)~7 nM) (PubMed:11755529, PubMed:11864985, PubMed:16497878, PubMed:17369411, PubMed:20600425), rERG1 (reversible, Kd=6.8 nM) (PubMed:16497878), rERG2 (irreversible, Kd=2.8 nM) (PubMed:16497878), hERG3 (irreversible, Kd=4.05 nM) (PubMed:16497878) and rERG3 (reversible, Kd=38.1 nM) (PubMed:16497878) potassium channels. The toxin potency is not affected by elevating potassium ion concentration from 2 to 98 mM (PubMed:11864985). This toxin only blocks channels in a closed state (PubMed:12860380). At high toxin concentrations, block of Kv11.1/KCNH2/ERG1 macroscopic current is incomplete (93.5%). This suggests a kinetic mechanism model with two different states of toxin-channel binding (T+C=TC*=TC in the TC* state, the toxin binds the channel but does not occlude the pore, whereas in the TC state the toxin binds and occludes the pore). In this model, incomplete block is explained by the relatively fast dissociation rate from the blocked channel conformation (TC) relative to the rate of conversion of the toxin-channel encounter complex (TC*) to the blocked channel conformation (TC) (PubMed:17369411). {ECO:0000269|PubMed:10224238, ECO:0000269|PubMed:11755529, ECO:0000269|PubMed:11864985, ECO:0000269|PubMed:12860380, ECO:0000269|PubMed:16497878, ECO:0000269|PubMed:17369411, ECO:0000269|PubMed:20600425}.

Target

voltage-gated potassium channel (Kv)

Source & Reference

NA
UniProtKB/Swiss-Prot Tox-Prot

Other

Centruroides noxius (Mexican scorpion)
Neurotoxin Ion channel impairing toxin Potassium channel impairing toxin Voltage-gated potassium channel impairing toxin
Blocks human and rat Kv11.1/KCNH2/ERG1 and Kv11.3/KCNH7/ERG3, as well as rat (but not human) Kv11.2/KCNH6/ERG2 (PubMed:11755529, PubMed:11864985, PubMed:16497878, PubMed:17369411, PubMed:20600425) by binding to channel outer vestibule (S5P domain) with a 1:1 stoichiometry (PubMed:11755529, PubMed:11864985, PubMed:17369411, PubMed:20600425). Inhibition data are the following: hERG1 (reversible, IC(50)~7 nM) (PubMed:11755529, PubMed:11864985, PubMed:16497878, PubMed:17369411, PubMed:20600425), rERG1 (reversible, Kd=6.8 nM) (PubMed:16497878), rERG2 (irreversible, Kd=2.8 nM) (PubMed:16497878), hER
Potassium channel toxin gamma-KTx 1.1 (Ergtoxin) (CnErg1) (CnErgTx1) (ErgTx) (ErgTx1)
scorpion
Ergtoxin family, Gamma-KTx 1 subfamily
Evidence at protein level
3D-structure Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Potassium channel impairing toxin Secreted Signal Toxin Voltage-gated potassium channel impairing toxin
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
Additional Detail Fields 7 fields
3D-structure Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Potassium channel impairing toxin Secreted Signal Toxin Voltage-gated potassium channel impairing toxin
Neurotoxin Ion channel impairing toxin Potassium channel impairing toxin Voltage-gated potassium channel impairing toxin
Evidence at protein level
Ergtoxin family, Gamma-KTx 1 subfamily
Potassium channel toxin gamma-KTx 1.1 (Ergtoxin) (CnErg1) (CnErgTx1) (ErgTx) (ErgTx1)
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
scorpion