Forespore Foursome

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Science  30 Apr 2004:
Vol. 304, Issue 5671, pp. 651
DOI: 10.1126/science.304.5671.651b

Proteases catalyze the addition of water across the peptide bond and hence, until recently, were thought to operate in an aqueous milieu. The discovery of intramembrane proteolysis in a wide range of contexts, from cleavage of the amyloid precursor protein implicated in Alzheimer's disease to developmental signaling via the Notch receptor in Drosophila, has stoked interest in finding out how such proteolysis occurs and what the active site looks like. Zhou and Kroos take a step toward these goals in a mutational analysis of the interaction between the protease, in this instance, a Zn-metalloenzyme called SpoIVFB, and its regulatory inhibitor BofA. These are part of a complex in the Bacillus subtilis forespore that releases a signal, the transcription factor σκ, into the mother cell compartment; the inactive precursor Pro-σκ is anchored in the forespore membrane and is the substrate of SpoIVFB. These authors propose that a histidine residue of BofA provides the fourth ligand to the active site Zn (with the other three contributed by SpoIVFB) and that destabilization of the BofA-SpoIVFB interaction moves the histidine away, allowing for activation of a nucleophilic water molecule by the Zn atom. — GJC

Proc. Natl. Acad. Sci. U.S.A. 101, 6385 (2004).

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