ISSN:
1573-3904
Keywords:
Zinc endopeptidase
;
Clostridial neurotoxins
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The light chain of tetanus neurotoxin (TeNT L chain)has been shown to be endowed with zinc endopeptidaseactivity, selectively directed towards theGln76–Phe77 bond of synaptobrevin, avesicle-associated membrane protein criticallyinvolved in neuroexocytosis. In previous reports,truncations at the NH2- and COOH-terminus ofsynaptobrevin have shown that the sequence 39–88 ofsynaptobrevin is the minimum substrate of TeNT,suggesting either the requirement of a well-definedthree-dimensional structure of synaptobrevin or a rolein the mechanism of substrate hydrolysis for residuesdistal from the cleavage site. In this study, theaddition of NH2- and COOH-terminal peptides ofsynaptobrevin, S 27–55 (S1) and S 82–93(S2), to the synaptobrevin fragment S 56–81allowed the cleavage of this latter peptide by TeNT tooccur. This appears to result from an activationprocess mediated by the simultaneous binding ofS1 and S2 with complementary sites presenton TeNT as shown by surface plasmon resonanceexperiments. All these results favor anexosite-controlled hydrolysis of synaptobrevin by TeNTprobably involving a conformational change of thetoxin. This could account for the high degree ofsubstrate specificity of TeNT and, probably, botulinumneurotoxins.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008822800144
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