TABLE 5

Properties of ASIC-targeting toxins

Psalmotoxin 1APETx2Mit-Toxin (act)Mambalgin-1a
OriginPsalmopoeus cambridgeiAnthopleura elegantissimaMicrurus tener tenerDendroaspis polylepis polylepis
FoldInhibitor cystine knotAll-β toxinKunitz type (MitTx-α) and phospholipase A2–like protein (MitTx-β)Three-finger toxin
Number of amino acids4042Dimer of MitTx-α: 60 MitTx-β: 11957
ASIC targetASIC1aASIC3All homomeric ASICsASIC1a and ASIC1b and many ASIC1a-containing heteromers
ASIC1a/2bASIC3-containing heteromers
ASIC1b (act)Nav1.8
cASIC1 (act)
Typical IC50 or EC50r/hASIC1a: 0.4–13 nMrASIC3: 37–63 nMrASIC1a: 9 nMrASIC1a: 55 nM
rASIC1a/3b: 3 nMrASIC2b/3: 117 nMrASIC1b: 23 nMrASIC1b: 192 nM
rASIC1b: 100 nMrASIC1a/3: 2 μMrASIC3: 830 nMrASIC1a/2a: 246 nM
cASIC1: 189 nMTTX-R Nav: 2.6 μM
Binding siteAcidic pocket/thumb helixUnknownWrist, palm, and thumbAcidic pocket
EffectInhibition/activationInhibitionActivation or potentiation (ASIC2a)Inhibition
MechanismAlkaline shift in the SSD (→inhibition) and/or activation pH dependence (→ activation)UnknownUnknownAcidic shift of the pH dependence of activation
  • act, activation.

  • a Mambalgin-2 from Dendroaspis polylepis polylepis and Mambalgin-3 from Dendroaspis angusticeps differ each in a single residue from Mambalgin-1 (Baron et al., 2013). For references, see text.