Mambalgin-1

UniProtKB accession:  P0DKR6

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UniProtKB description:  This three-finger toxin inhibits ASIC channels. It acts as a gating modifier toxin by decreasing the apparent proton sensitivity of activation and by slightly increasing the apparent proton sensitivity for inactivation (PubMed:23034652). It binds more tightly to the closed state and to a much lesser extent the inactivated/desensitized state of ASIC1a isoform of ASIC1 (PubMed:23034652). It interacts directly with the outside surface of the thumb domain of chicken ASIC1a (ASIC1a), but does not insert into the acidic pocket as suggested for mambalgin-2 (PubMed:29872539). This binding leads to relocation of the thumb domain that could disrupt the acidic pocket of cASIC1a (PubMed:29872539). It reversibly inhibits rat ASIC1a (IC(50)=3.4-55 nM), rat ASIC1a-ASIC2b (IC(50)=61 nM), rat ASIC1a-ASIC1b (IC(50)=72 nM), human ASIC1a (IC(50)=127-580 nM), chicken ASIC1a (IC(50)=123.6 nM), rat ASIC1b (IC(50)=22.2-203 nM), rat ASIC1a-ASIC2a (IC(50)=152-252 nM) (PubMed:23034652, PubMed:23624383, PubMed:25873388, PubMed:24619065, PubMed:26680001, PubMed:29872539). In vivo, it shows a potent naloxone-resistant analgesic effect against acute and inflammatory pain upon central and peripheral injection (PubMed:23034652). In addition, it also has an opioid-independent effect on both thermal and mechanical inflammatory pain after systemic administration and is effective against neuropathic pain (PubMed:26680001).