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  • Title: m1-toxin isotoxins from the green mamba (Dendroaspis angusticeps) that selectively block m1 muscarinic receptors.
    Author: Carsi JM, Potter LT.
    Journal: Toxicon; 2000 Feb; 38(2):187-98. PubMed ID: 10665800.
    Abstract:
    The venom of the green mamba, Dendroaspis angusticeps, was found to have at least six trace m1-specific toxins that block the binding of 3H-N-methylscopolamine to cloned m1 muscarinic receptors. Four were isolated by gel filtration, cation exchange HPLC and reversed-phase HPLC and named m1-toxins1-4. Recovery was 180, 90, 20 and 10 microg/g dry venom, respectively. m1-Toxin1 (the original m1-toxin) was found to have the sequence, L T C V K S N S I W F P T S E D C P D G Q N LC F K R W Q Y I S P R M Y D F T R G C A A T C P K A E Y R D V I N C C G T D K C N K, calculated mass = 7473 Da and calculated pI = 8.2. This sequence had been predicted previously from a cDNA cloned from the venom glands of this snake. The binding of m1-toxin1 was irreversible, so its Kd could not be determined. m1-Toxin2 differed only in proline-19, mass = 7455 and pI = 8.5. Partial sequence data for m1-toxin3 showed aspartate-7 and m1-toxin4 showed isoleucine-12, asparagine-16 and alanine-19. m1-Toxins1-4 have seven conserved amino acids not found in homologous mamba toxins that bind to other muscarinic receptors (MT1, MT2, m4-toxin = MT3, MT4, MT5, MTalpha and MTbeta). Some of these residues may be essential for m1-specificity. Since m1-toxin1 binds irreversibly in artificial cerebrospinal fluid at 37 degrees C, it is a particularly attractive antagonist for studies in vivo.
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