Two-site autoinhibition of the ADP-ribosylating mosquitocidal toxin (MTX) from Bacillus sphaericus by its 70-kDa ricin-like binding domain

Biochemistry
Irina CarpuscaKlaus Aktories

Abstract

The mosquitocidal toxin (MTX) from Bacillus sphaericus SSII-1 is an approximately 97-kDa arginine-specific ADP-ribosyltransferase that is activated by proteolytic cleavage, thereby releasing the active 27-kDa enzyme (MTX(30-264)) and a 70-kDa C-terminal fragment (MTX(265-870)). In solution, the cleaved 70-kDa fragment is still a potent inhibitor of the ADP-ribosyltransferase activity of MTX. Here we studied the interaction of the 70-kDa fragment with the enzyme domain of MTX. Several C-terminal deletions of the 70-kDa fragment inhibited the enzymatic activity of MTX(30-264). However, the IC(50) values were about 2 orders of magnitude higher for the deletions than for the 70-kDa fragment. A peptide covering amino acid residues 265-285 of the holotoxin exhibited the same inhibitory potency as the C-terminal deletions of the 70-kDa fragment. MTX(265-285) contains several acidic residues, of which D273 and D275 were found to be essential for the inhibitory effect. Exchange of these residues in the 70-kDa fragment (MTX(265-870)) reduced its inhibitory potency. Kinetic analysis showed that the peptide MTX(265-285) had no effect on the V(max) of MTX(30-264) but increased the K(m) for NAD. By contrast, the 70-kDa fragment deleted of re...Continue Reading

References

Aug 1, 1992·Journal of Bacteriology·T ThanabaluC Berry
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Oct 1, 1994·Molecular Microbiology·M DomenighiniR Rappuoli
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Mar 21, 2003·The Journal of Biological Chemistry·Yuko Matsushima-HibiyaKeiji Wakabayashi

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Citations

Feb 18, 2006·Journal of Molecular Biology·Dirk J ReinertGeorg E Schulz
Nov 30, 2010·Toxicon : Official Journal of the International Society on Toxinology·Joachim H C OrthKlaus Aktories
Jul 1, 2008·Journal of Molecular Biology·Nora TreiberGeorg E Schulz
Dec 6, 2012·Toxicon : Official Journal of the International Society on Toxinology·Tsuyoshi NakanoYukari Totsuka

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