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Peptide record

TPDB72186

Neurotoxin standard
74 amino acids
Basic Information
3D PDB MODEL
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TPDB72186
Neurotoxin
Toxicity and safety peptides
NTxPred2
standard
No
A 74-aa standard natural neurotoxin peptide sequence curated from NTxPred2, with an available 3D structural model.
Sequence
MKLTCVLIITVLFLTACQLTTAVTYSRGEHKHRALMSTGTNYRLPKTCRSSGRYCRSPYDRRRRYCRRITDACV
Physicochemical Analysis
C369H613N119O103S8
W
R
8621.14
10.47
17
3
26
+12
10.09
-0.349
73.78
Mammalian: 30 hour Yeast: >20 hour E.coli: >10 hour
7825
90.77
28
Residue Composition
number
4
A
12
R
1
N
2
D
6
C
1
E
1
Q
3
G
2
H
3
I
7
L
3
K
2
M
1
F
2
P
5
S
10
T
0
W
5
Y
4
V
Amino Acid Distribution
A: 4 R: 12 N: 1 D: 2 C: 6 E: 1 Q: 1 G: 3 H: 2 I: 3 L: 7 K: 3 M: 2 F: 1 P: 2 S: 5 T: 10 W: 0 Y: 5 V: 4
Chemical Descriptors
74
C369H613N119O103S8
8621.14
10.47
+12
10.09
-0.349
Evidence Records 1 records
Evidence 1 Activity

Activity

Neurotoxin
FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin is very potent on alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR (IC(50)=4.61-12 nM for the bead isomer (I-II III-IV), IC(50)=7-16 nM for the ribbon isomer (I-IV II-III) and IC(50)=22.7 nM for the globular isomer (I-III II-IV)) (PubMed:26170295, PubMed:31986036). The bead isomer also shows a weak inhibition on other nAChRs (alpha-1-beta-1-delta-epsilon/CHRNA1-CHRNB1-CHRND-CHRNE, alpha-7/CHRNA7, alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3), alpha-3-beta-2/CHRNA3-CHRNB2, alpha-2-beta-2/CHRNA2-CHRNB2, alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4), alpha-4-beta-2/CHRNA4-CHRNB2, alpha-4-beta-4/CHRNA4-CHRNB4, alpha-2-beta-4/CHRNA2-CHRNB4, alpha-3-beta-4/CHRNA3-CHRNB4) (PubMed:26170295, PubMed:31986036). The toxin blockade is voltage-dependent, and its binding site does not overlap with the binding site of the competitive antagonist alpha-conotoxin RgIA (PubMed:26170295). The toxin inhibits Sf9 cell growth (PubMed:22825834). Both the bead and ribbon isomers relieve pain effects in the rat chronic constriction injury (CCI) model of neuropathic pain, and in the acute pain model of tail flick test, but have no effect on motor performance (PubMed:26170295, PubMed:26706456). {ECO:0000269|PubMed:22825834, ECO:0000269|PubMed:26170295, ECO:0000269|PubMed:26706456, ECO:0000269|PubMed:31986036}.

Target

nicotinic acetylcholine receptor (nAChR) acetylcholine receptor

Source & Reference

NA
UniProtKB/Swiss-Prot Tox-Prot

Other

Conus generalis (General cone)
Neurotoxin Postsynaptic neurotoxin Acetylcholine receptor inhibiting toxin
Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin is very potent on alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR (IC(50)=4.61-12 nM for the bead isomer (I-II III-IV), IC(50)=7-16 nM for the ribbon isomer (I-IV II-III) and IC(50)=22.7 nM for the globular isomer (I-III II-IV)) (PubMed:26170295, PubMed:31986036).
Alpha-conotoxin GeXIVA (Alpha-O-conotoxin GeXIVA) (Conotoxin Ge14.1) (Conotoxin GeXIVAWT)
cone snail
Conotoxin O1 superfamily
Evidence at protein level
Acetylcholine receptor inhibiting toxin Disulfide bond Neurotoxin Pharmaceutical Postsynaptic neurotoxin Secreted Signal Toxin
TISSUE SPECIFICITY: Expressed by the venom duct. {ECO:0000305|PubMed:22825834}.
Additional Detail Fields 7 fields
Acetylcholine receptor inhibiting toxin Disulfide bond Neurotoxin Pharmaceutical Postsynaptic neurotoxin Secreted Signal Toxin
Neurotoxin Postsynaptic neurotoxin Acetylcholine receptor inhibiting toxin
Evidence at protein level
Conotoxin O1 superfamily
Alpha-conotoxin GeXIVA (Alpha-O-conotoxin GeXIVA) (Conotoxin Ge14.1) (Conotoxin GeXIVAWT)
TISSUE SPECIFICITY: Expressed by the venom duct. {ECO:0000305|PubMed:22825834}.
cone snail