O-Aryloxycarbonyl hydroxamates and 1,3,4-oxathiazol-2-ones have been identified as covalent inhibitors of β-lactamases and proteasomes, respectively. The products of these inhibition reactions are remarkably similar, involving carbonyl cross-linking of the active sites. We have cross-checked these inhibitors, showing that the former inhibit proteasomes and the latter β-lactamases, to form the same inactive carbonyl adducts. These results are discussed in terms of similarities of the active site structures and catalytic mechanisms. It is likely that a mechanistic imperative has led to convergent evolution of these enzyme active sites, of a β-lactam-recognizing enzyme and a N-terminal protease belonging to different amidohydrolase superfamilies.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505995PMC
http://dx.doi.org/10.1016/j.febslet.2012.10.019DOI Listing

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